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We present our initial experience of ultrasound (US)-guided localization of clipped metastatic axillary lymph nodes (LNs) following neoadjuvant chemotherapy (NAC). We evaluated US visibility and the successful excision rate of clipped LN after NAC in 29 consecutive patients with breast cancer. US-guided localization of clipped nodes was performed in 22 patients on the day of surgery, while seven patients underwent surgery without localization. The clips were identified in all patients with residual metastatic LNs and 6 of 12 (50%) patients without residual metastatic LNs on US. Six patients without visible clips underwent US-guided localization at the presumed previous clip insertion site. The successful excision rate of 22 LNs with localization was 100% (even though 3 of them were non-sentinel LNs) and 57% (4/7) without localization. Regardless of the presence of visible residual metastatic LNs on US after NAC, successful excision of the clipped LN with US-guided localization is feasible.
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Purpose@#The purpose of this study was to investigate the concordance rate of PIK3CA mutations between primary and matched distant metastatic sites in patients with breast cancer and to verify whether there are differences in the frequency of PIK3CA hotspot mutations depending on the metastatic sites involved. @*Materials and Methods@#Archived formalin-fixed paraffin-embedded (FFPE) specimens of primary breast and matched distant metastatic tumors were retrospectively obtained for 49 patients. Additionally, 40 archived FFPE specimens were independently collected from different breast cancer metastatic sites, which were limited to three common sites: the liver, brain, and lung. PIK3CA mutations were analyzed using droplet digital PCR, including hotspots involving exons 9 and 20. @*Results@#After analysis of 49 breast tumors with matched metastasis sites, 87.8% showed concordance in PIK3CA mutation status. According to PIK3CA hotspot mutation testing in 89 cases of breast cancer metastatic sites, the proportion of PIK3CA mutations at sites of metastasis involving the liver, brain, and lung was 37.5%, 28.6%, and 42.9%, respectively, which did not result in statistical significance. @*Conclusion@#The high concordance of PIK3CA mutation status between primary and matched metastasis sites suggests that metastatic sites, regardless of the metastatic organ, could be considered sample sources for PIK3CA mutation testing for improved therapeutic strategies in patients with metastatic breast cancer.
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Purpose@#The GenesWell™ breast cancer test (BCT) is a recently developed multigene assay that predicts the risk of distant recurrence in patients with hormone receptor-positive (HR+) and human epidermal growth factor-2 negative (HER2−) early breast cancer (BC). The ability of this assay to predict the response to neoadjuvant chemotherapy (NACT) has not been established to date. @*Methods@#Biopsy specimens from HR+/HER2− BC patients with axillary lymph node (LN) metastasis who underwent NACT were analyzed using the BCT score. The modified BCT score was developed and patients classified into high-and low-response groups. A total of 88 patients were available for the BCT score among the 108 eligible patients. The median followup duration was 35.9 (7.8–128.5) months. @*Results@#Among them, 61 (65.1%) had cN1 and 53 (60.2%) had cT1 or cT2 disease. The BCT score was low in 25 (28.4%) patients and high in 63 (71.6%). Among the 50 patients with pathologic complete response or partial response, 41 (82.0%) were in the high BCT score group and 9 (18.0%) were in the low BCT score group. Among the 38 patients with stable or progressive disease, 22 (57.9%) were in the high BCT score group and 16 (42.1%) were in the low BCT score group (p = 0.025). Ki-67 before NACT was a significant factor for predicting tumor response (p = 0.006; 3.81 [1.50–10.16]). The BCT score showed a significant response to NACT (p = 0.016; 4.18 [1.34–14.28]). Distant metastasis-free survival was significantly different between the high- and low-response groups (p = 0.004). @*Conclusion@#We demonstrated that the BCT score predicts NACT responsiveness in HR+/ HER2− BC with LN metastasis and might help determine whether NACT should be performed. Further studies are required to validate these results.
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Purpose@#To determine the incidence of atypical ductal hyperplasia (ADH) in needle biopsy and the upgrade rate to carcinoma, and to evaluate difference in findings between the upgrade and non-upgrade groups. @*Materials and Methods@#Among 9660 needle biopsies performed over 48 months, we reviewed the radiologic and histopathologic findings of ADH and compared the differences in imaging findings (mammography and breast US) and biopsy methods between the upgrade and non-upgrade groups. @*Results@#The incidence of ADH was 1.7% (169/9660). Of 112 resected cases and 30 cases followed-up for over 2 years, 35 were upgraded to carcinoma (24.6%, 35/142). The upgrade rates were significantly different according to biopsy methods: US-guided core needle biopsy (US-CNB) (40.7%, 22/54) vs. stereotactic-vacuum-assisted biopsy (S-VAB) (16.0%, 12/75) vs. US-guided VAB (US-VAB) (7.7%, 1/13) (p = 0.002). Multivariable analysis showed that only US-CNB (odds ratio = 5.19, 95% confidence interval: 2.16–13.95, p < 0.001) was an independent predictor for pathologic upgrade. There was no upgrade when a sonographic mass was biopsied by US-VAB (n = 7) @*Conclusion@#The incidence of ADH was relatively low (1.7%) and the upgrade rate was 24.6%. Surgical excision should be considered because of the considerable upgrade rate, except in the case of US-VAB.
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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.
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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.
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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.
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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.
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Background@#Pure mucinous carcinoma (PMC) is a rare type of breast cancer, estimated to represent 2% of invasive breast cancer. PMC is typically positive for estrogen receptors (ER) and progesterone receptors (PR) and negative for human epidermal growth factor receptor 2 (HER2). The clinicopathologic characteristics of HER2-positive PMC have not been investigated. @*Methods@#Pathology archives were searched for PMC diagnosed from January 1999 to April 2018. Clinicopathologic data and microscopic findings were reviewed and compared between HER2-positive PMC and HER2-negative PMC. We also analyzed the differences in disease-free survival (DFS) and overall survival according to clinicopathologic parameters including HER2 status in overall PMC cases. @*Results@#There were 21 HER2-positive cases (4.8%) in 438 PMCs. The average tumor size of HER2-positive PMC was 32.21 mm (± 26.55). Lymph node metastasis was present in seven cases. Compared to HER2-negative PMC, HER2-positive PMC presented with a more advanced T category (p < .001), more frequent lymph node metastasis (p = .009), and a higher nuclear and histologic grade (p < .001). Microscopically, signet ring cells were frequently observed in HER2-positive PMC (p < .001), whereas a micropapillary pattern was more frequent in HER2-negative PMC (p = .012). HER2-positive PMC was more frequently negative for ER (33.3% vs. 1.2%) and PR (28.6% vs. 7.2%) than HER2-negative PMC and showed a high Ki-67 labeling index. During follow-up, distant metastasis and recurrence developed in three HER2-positive PMC patients. Multivariate analysis revealed that only HER2-positivity and lymph node status were significantly associated with DFS. @*Conclusions@#Our results suggest that HER2-positive PMC is a more aggressive subgroup of PMC. HER2 positivity should be considered for adequate management of PMC.
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PURPOSE@#To evaluate the criteria for predicting invasive lesions with preoperative breast MRI in ductal carcinoma in situ (DCIS) histopathologically diagnosed with biopsy.@*MATERIALS AND METHODS@#We retrospectively analyzed the preoperative MRI findings of 80 percutaneous biopsy-proven DCIS. The morphological type, enhancement distribution and kinetics, and extent of the lesions were analyzed. We compared the results of pure DCIS and DCIS with invasive lesions. We evaluated the MRI criteria for predicting DCIS with invasive lesions and assessed its diagnostic performance.@*RESULTS@#Of the 80 DCIS lesions analyzed, 27 contained co-existing invasive lesions and 49 were pure DCIS. No residual lesions after biopsy were seen in 4 cases. DCIS with invasive lesions showed washout kinetics more frequently and to a larger extent than did pure DCIS (p = 0.030 and p = 0.048, respectively). Using enhancement kinetics and the lesion cut-off value of 4 cm yielded the highest diagnostic performance, with 92.6% sensitivity and 93.8% negative predictive value for predicting invasive lesions.@*CONCLUSION@#Washout kinetics and the lesion extent of at least 4 cm are useful criteria for the prediction of co-existing invasive lesions in patients with DCIS diagnosed with biopsy.
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Mucinous carcinoma (MC) is a rare subtype of breast cancer, which is composed of tumor cells floating in the abundant extracellular mucin. This form of cancer is usually estrogen receptor/progesterone receptor positive and human epidermal growth factor receptor 2 (HER2) negative. Here, we present a case of HER2-positive MC with an unusual signet ring cell differentiation. It is very rare that a breast tumor consists entirely of signet ring cells. The tumor showed pathologic complete response (pCR) after neoadjuvant chemotherapy with trastuzumab and pertuzumab. pCR of HER2-positive MC has rarely been described in literature. It is important to consider the biological heterogeneity of MCs for effective management.
Subject(s)
Humans , Adenocarcinoma, Mucinous , Breast Neoplasms , Carcinoma, Signet Ring Cell , Cell Differentiation , Drug Therapy , Epidermal Growth Factor , Estrogens , Mucins , Neoadjuvant Therapy , Polymerase Chain Reaction , Population Characteristics , ErbB Receptors , Receptor, ErbB-2 , TrastuzumabABSTRACT
Perivascular epithelioid cell tumor (PEComa) is a very rare mesenchymal tumor with a distinctive morphology and immunophenotype. PEComas usually harbor TSC2 alterations, although TFE3 translocations, which occur in MiT family translocation renal cell carcinoma and alveolar soft part sarcoma, are also possible. We recently experienced a case of PEComa with TFE3 expression arising in the breast. An 18-year-old female patient presented with a right breast mass. Histologically, the tumor consisted of epithelioid cells with alveolar structure and showed a diffuse strong expression of HMB45 and TFE3. TSC2 was preserved. Melan A and smooth muscle actin were negative. To our knowledge, this is the first Korean case of PEComa of the breast that intriguingly presented with TFE3 expression.
Subject(s)
Adolescent , Female , Humans , Actins , Breast , Carcinoma, Renal Cell , Epithelioid Cells , MART-1 Antigen , Muscle, Smooth , Perivascular Epithelioid Cell Neoplasms , Sarcoma, Alveolar Soft PartABSTRACT
PURPOSE: PIK3CA mutation is considered to be a possible cause for resistance to neoadjuvant chemotherapy (NAC) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We investigated the association between PIK3CA mutations and the outcome of NAC in HER2-positive breast cancers. METHODS: A total of 100 HER2-positive breast cancer patients who had undergone NAC and surgery between 2004 and 2016 were examined. Mutation status was sequentially assessed in pre-NAC, post-NAC, and recurrent specimens taken from these patients. RESULTS: PIK3CA mutations were identified in the sequential specimens of 17 patients (17.0%). These 17 patients experienced shorter disease-free survival (DFS) than the rest of the patients (58.3 months vs. 119.3 months, p=0.020); however, there was no significant difference in pathologic complete response (pCR) and overall survival (OS) (pCR, 17.6% vs. 33.7%, p=0.191; OS, 84.5 months vs. 118.0 months, p=0.984). While there was no difference in pCR between the wild-type and mutant PIK3CA groups in pre-NAC specimens (25.0% vs. 31.8%, p=0.199), PIK3CA mutations correlated with lower pCR in post-NAC specimens (0.0% vs. 24.3%, p < 0.001). Multivariate analysis revealed significantly worse DFS in the mutant PIK3CA group than in the wild-type group (hazard ratio, 3.540; 95% confidence interval, 1.001–12.589; p=0.050). Moreover, the DFS curves of the change of PIK3CA mutation status in sequential specimens were significantly different (p=0.016). CONCLUSION: PIK3CA mutation in HER2-positive breast cancer was correlated with a lower pCR rate and shorter DFS. These results suggest that PIK3CA mutation is a prognostic marker for NAC in HER2-positive breast cancer, especially in post-NAC specimens.
Subject(s)
Humans , Humans , Breast , Breast Neoplasms , Disease-Free Survival , Drug Therapy , Epidermal Growth Factor , Multivariate Analysis , Neoadjuvant Therapy , Phosphatidylinositol 3-Kinases , Polymerase Chain Reaction , ErbB Receptors , Receptor, ErbB-2ABSTRACT
BACKGROUND: In the current American Joint Committee on Cancer staging system of breast cancer, only tumor size determines T-category regardless of whether the tumor is single or multiple. This study evaluated if tumor multiplicity has prognostic value and can be used to subclassify breast cancer. METHODS: We included 5,758 patients with invasive breast cancer who underwent surgery at Samsung Medical Center, Seoul, Korea, from 1995 to 2012. RESULTS: Patients were divided into two groups according to multiplicity (single, n = 4,744; multiple, n = 1,014). Statistically significant differences in lymph node involvement and lymphatic invasion were found between the two groups (p < .001). Patients with multiple masses tended to have luminal A molecular subtype (p < .001). On Kaplan-Meier survival analysis, patients with multiple masses had significantly poorer disease-free survival (DFS) (p = .016). The prognostic significance of multiplicity was seen in patients with anatomic staging group I and prognostic staging group IA (p = .019 and p = .032, respectively). When targeting patients with T1-2 N0 M0, hormone receptor–positive, and human epidermal growth factor receptor 2 (HER2)–negative cancer, Kaplan-Meier survival analysis also revealed significantly reduced DFS with multiple cancer (p = .031). The multivariate analysis indicated that multiplicity was independently correlated with worse DFS (hazard ratio, 1.23; 95% confidence interval, 1.03 to 1.47; p = .025). The results of this study indicate that tumor multiplicity is frequently found in luminal A subtype, is associated with frequent lymph node metastasis, and is correlated with worse DFS. CONCLUSIONS: Tumor multiplicity has prognostic value and could be used to subclassify invasive breast cancer at early stages. Adjuvant chemotherapy would be necessary for multiple masses of T1–2 N0 M0, hormone-receptor-positive, and HER2-negative cancer.
Subject(s)
Humans , Breast Neoplasms , Breast , Chemotherapy, Adjuvant , Disease-Free Survival , Joints , Korea , Lymph Nodes , Multivariate Analysis , Neoplasm Metastasis , Neoplasm Staging , Phenobarbital , Prognosis , ErbB Receptors , SeoulABSTRACT
BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) has been associated with favorable clinical outcome in breast cancer patients. However, the possibility that the prognostic significance of pCR differs among various definitions has not been established. METHODS: We retrospectively evaluated the pathologic response after NAC in 353 breast cancer patients and compared the prognoses after applying the following different definitions of pCR: ypT0/is, ypT0, ypT0/is ypN0, and ypT0 ypN0. RESULTS: pCR was significantly associated with improved distant disease-free survival (DDFS) regardless of the definition (ypT0/is, p = .002; ypT0, p = .008; ypT0/is ypN0, p < .001; ypT0 ypN0, p = .003). Presence of tumor deposits of any size in the lymph nodes (LNs; ypN ≥ 0(i+)) was associated with worse DDFS (ypT0 ypN0 vs ypT0 ypN ≥ 0(i+), p = .036 and ypT0/is ypN0 vs ypT0/is ypN ≥ 0(i+), p = .015), and presence of isolated tumor cells was associated with decreased overall survival (OS; ypT0/is ypN0 vs ypT0/is ypN0(i+), p = .013). Residual ductal carcinoma in situ regardless of LN status showed no significant difference in DDFS or OS (DDFS: ypT0 vs ypTis, p = .373 and ypT0 ypN0 vs ypTis ypN0, p = .462; OS: ypT0 vs ypTis, p = .441 and ypT0 ypN0 vs ypTis ypN0, p = .758). In subsequent analysis using ypT0/is ypN0, pCR was associated with improved DDFS and OS in triple-negative tumors (p < .001 and p = .003, respectively). CONCLUSIONS: Based on our study results, the prognosis and rate of pCR differ according to the definition of pCR and ypT0/is ypN0 might be considered a more preferable definition of pCR.
Subject(s)
Humans , Breast Neoplasms , Breast , Carcinoma, Intraductal, Noninfiltrating , Disease-Free Survival , Drug Therapy , Lymph Nodes , Polymerase Chain Reaction , Prognosis , Retrospective StudiesABSTRACT
PURPOSE: Accurate testing for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) is essential for breast cancer treatment. At present, immunohistochemistry (IHC)/florescence in situ hybridization (FISH) are widely accepted as the standard testing methods. To investigate the value of NanoString nCounter®, we performed its comparative analysis with IHC/FISH and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) for the assessment of ER, PR, and HER2. METHODS: Data on IHC/FISH results for ER, PR, and HER2 in 240 patients from a single tertiary hospital in Korea were collected and compared with NanoString nCounter® and qRT-PCR results at a single institution. RESULTS: Expression levels for each gene using NanoString nCounter® showed good correlation with the corresponding data for protein expression by IHC (p<0.001) and gene amplification status for HER2 (p<0.001). Comparisons between gene expression and IHC data showed good overall agreement with a high area under the curve (AUC) for ESR1/ER (AUC=0.939), PgR/PR (AUC=0.796), and HER2/HER2 (AUC=0.989) (p<0.001). CONCLUSION: The quantification of ER, PgR, and HER2 mRNA expression with NanoString nCounter® may be a viable alternative to conventional IHC/FISH methods.
Subject(s)
Humans , Breast Neoplasms , Breast , Estrogens , Gene Amplification , Gene Expression , Immunohistochemistry , In Situ Hybridization , Korea , Polymerase Chain Reaction , Real-Time Polymerase Chain Reaction , ErbB Receptors , Receptors, Progesterone , Reverse Transcription , RNA, Messenger , Tertiary Care CentersABSTRACT
Primary mucinous cystadenocarcinoma (MCA) of the breast is a rare but pathologically distinct breast tumor. There have been some case reports on primary MCA of the breast; however, they have all focused on pathologic findings. Here, we report the radiologic findings of two cases of MCA along with a review of the literature. Breast MCA shows a circumscribed mass with some calcifications on mammography, an intracystic solid mass without increased vascularity or a vascular stalk on ultrasound, and a heterogeneously enhancing mass within a rim-enhancing cyst with intermediate signal intensity on T2-weighted magnetic resonance imaging. These radiologic findings and the presence of mucin in the percutaneous biopsy specimen should suggest the possibility of MCA in the differential diagnosis of a breast tumor.