Hee-Chul Shin

Breast density change as a predictive surrogate for response to adjuvant endocrine therapy in hormone receptor positive breast cancer

IntroductionAnti-estrogen therapy has been shown to reduce mammographic breast density (MD). We hypothesized that a short-term change in breast density may be a surrogate biomarker predicting response to adjuvant endocrine therapy (ET) in breast cancer.MethodsWe analyzed data for 1,065 estrogen receptor (ER)-positive breast cancer patients who underwent surgery between 2003 and 2006 and received at least 2 years of ET, including tamoxifen and aromatase inhibitors. MD was measured using Cumulus software 4.0 and expressed as a percentage. MD reduction (MDR) was defined as the absolute difference in MD of mammograms taken preoperatively and 8-20 months after the start of ET.ResultsAt a median follow-up of 68.8 months, the overall breast cancer recurrence rate was 7.5% (80/1065). Mean MDR was 5.9% (range, -17.2% to 36.9%). Logistic regression analysis showed that age < 50 years, high preoperative MD, and long interval between start of ET to follow-up mammogram were significantly associated with larger MDR (p < 0.05). In a survival analysis, tumor size, lymph node positivity, high Ki-67 (≥ 10%), and low MDR were independent factors significantly associated with recurrence-free survival (p < 0.05). Compared with the group showing the greatest MDR (≥ 10%), the hazard ratios for MDRs of 5-10%, 0-5%, and < 0% were 1.33, 1.92, and 2.26, respectively.ConclusionsMD change during short-term use of adjuvant ET was a significant predictor of long-term recurrence in women with ER-positive breast cancer. Effective treatment strategies are urgently needed in patients with low MDR despite about 1 year of ET.

Low rates of additional cancer detection by magnetic resonance imaging in newly diagnosed breast cancer patients who undergo preoperative mammography and ultrasonography.

Purpose We evaluated the efficacy of breast magnetic resonance imaging (MRI) for detecting additional malignancies in breast cancer patients newly diagnosed by breast ultrasonography and mammography. Methods We retrospectively reviewed the records of 1,038 breast cancer patients who underwent preoperative mammography, bilateral breast ultrasonography, and subsequent breast MRI between August 2007 and December 2010 at single institution in Korea. MRI-detected additional lesions were defined as those lesions detected by breast MRI that were previously undetected by mammography and ultrasonography and which would otherwise have not been identified. Results Among the 1,038 cases, 228 additional lesions (22.0%) and 30 additional malignancies (2.9%) were detected by breast MRI. Of these 228 lesions, 109 were suspected to be malignant (Breast Imaging-Reporting and Data System category 4 or 5) on breast MRI and second-look ultrasonography and 30 were pathologically confirmed to be malignant (13.2%). Of these 30 lesions, 21 were ipsilateral to the main lesion and nine were contralateral. Fourteen lesions were in situ carcinomas and 16 were invasive carcinomas. The positive predictive value of breast MRI was 27.5% (30/109). No clinicopathological factors were significantly associated with additional malignant foci. Conclusion Breast MRI was useful in detecting additional malignancy in a small number of patients who underwent ultrasonography and mammography.

Preoperative serum tissue polypeptide-specific antigen is a valuable prognostic marker in breast cancer

Tissue polypeptide‐specific antigen (TPS), a specific epitope structure of a peptide in serum associated with human cytokeratin 18, is linked to the proliferative activity of tumors. Here, we aimed to identify the association between the preoperative serum TPS level and outcome in breast cancer patients. We assayed preoperative serum TPS levels in 1,477 breast cancer patients treated between June 2000 and December 2006. The TPS level was measured with a one‐step solid phase radiometric sandwich assay detecting the M3 epitope on cytokeratin 18 fragments. The cutoff value was 80 U/L. Among the 1,477 breast cancer patients examined, preoperative serum TPS level was elevated (>80 U/L) in 290 patients (19.6%). Age (>45 years), tumor size (>2 cm), nodal metastasis, negative progesterone receptor and human epidermal growth factor receptor 2 were associated with elevated TPS. Evidence of recurrence was observed in 229 patients (15.6%). Elevated TPS was associated with poor disease‐free survival (p < 0.001) and overall survival (p < 0.001). In a multivariate analysis using the Cox proportional regression model, elevated TPS was an independent prognostic factor for disease‐free survival (p = 0.001) and overall survival (p = 0.026). Furthermore, in subgroup analysis based on molecular subtype, the prognostic effect of preoperative TPS on survival (OS: HR 2.614, p = 0.003; DFS: HR 1.895, p = 0.001) was identified only in the luminal A subtype. Elevated preoperative serum TPS level is associated with poor breast cancer outcomes. Based on these findings, we conclude that preoperative TPS is a valuable biomarker for clinical use in predicting outcomes in breast cancer patients.

A Pilot Study Evaluating Liquid-Based Fine Needle Aspiration Cytology of Breast Lesions: A Cytomorphological Comparison of SurePath® Liquid-Based Preparations and Conventional Smears

Objective: Fine needle aspiration cytology (FNAC) is recommended by the World Health Organization as a diagnostic method for breast lesions. The morphological interpretation of liquid-based preparations (LBPs) remains a diagnostic challenge due to considerably altered cytomorphology. The aim of the current study was to compare cytomorphological characteristics of SurePath® (SP)-based LBP and conventional smear (CS) in breast FNACs. Study Design: The study included 77 benign and 60 malignant breast FNACs obtained by both SP and CS, all with tissue confirmation. Cases analyzed with both preparations were reviewed and compared, focusing on 10 cytomorphological features. Results: SP aspirates demonstrated notable cytomorphological alterations. Among them, a prominent three-dimensional configuration of cell clusters and frequent and conspicuous nucleoli were the most prominent characteristics of SP compared with CS. Overall diagnostic performances were comparable but were slightly lower for SP than CS (diagnostic accuracy of two reviewers; 87.6 and 90.5% for SP vs. 91.2 and 92.7% for CS, respectively). Conclusion: Although the reviewer should be aware of distinctive cytomorphological alterations, the SP technique is reliable for the evaluation of breast lesions with the advantage of easy interpretation and a diagnostic accuracy equivalent to CS.

Sarcoidosis Mimicking Metastatic Breast Cancer in Korean Woman with Breast Cancer

*Department of Surgery, Chung-Ang University College of Medicine, Chung-Ang University Hospital, Seoul, Korea; Department of Thoracic and Cardiovascular Surgery, Chung-Ang University College of Medicine, Chung-Ang University Hospital, Seoul, Korea; Department of Pathology, Chung-Ang University College of Medicine, Chung-Ang University Hospital, Seoul, Korea; Department of Internal Medicine, Chung-Ang University College of Medicine, Chung-Ang University Hospital, Seoul, Korea; Department of Radiology, Chung-Ang University College of Medicine, Chung-Ang University Hospital, Seoul, Korea

Phosphorylation of p90RSK is associated with increased response to neoadjuvant chemotherapy in ER-positive breast cancer

BackgroundThe clinical implication of Ras/Raf/ERK pathway activity in breast cancer tissue and its association with response to chemotherapy is controversial. We aimed to explore the value of p90RSK phosphorylation, a downstram molecule of the pathway, in predicting chemotherapy response in breast cancer.MethodsThe expression of phosphorylated p90RSK (phospho-p90RSK) and chemotherapy response was measured in 11 breast cancer cell lines and 21 breast cancer tissues. The predictive value of phospho-p90RSK was validated in core needle biopsy specimens of 112 locally advanced breast cancer patients who received anthracycline and taxane-based neoadjuvant chemotherapy.ResultsIn 11 breast cancer cell lines, the relative expression of phospho-p90RSK was inversely correlated with cell survival after doxorubicin treatment (p = 0.021). Similar association was observed in fresh tissues from 21 breast cancer patients in terms of clinical response. In paraffin-embedded, formalin-fixed tissues from core needle biopsy tissues from 112 patients, positive phospho-p90RSK expression was associated with greater tumor shrinkage and smaller post-chemotherapy tumor size. The association between phospho-p90RSK expression and chemotherapy response was more evident in estrogen receptor(ER)-positive tumors. The expression of phosphor-p90RSK did not show a significant relationship with the incidence of pCR. P90RSK silencing using siRNA did not affect the cancer cell’s response to doxorubicin, and the expression of phospho-p90RSK was highly correlated with other Ras/Raf/ERK pathway activation.ConclusionOur results suggest that phospho-p90RSK expression, which reflects the tumor’s Ras/Raf/ERK/p90RSK pathway activation can be a potential predictive marker for chemotherapy response in ER-positive breast cancer which needs further independent validation.

Patients with Concordant Triple-Negative Phenotype between Primary Breast Cancers and Corresponding Metastases Have Poor Prognosis

Purpose We investigated the prognostic impact of discordance between the receptor status of primary breast cancers and corresponding metastases. Methods A total 144 patients with breast cancer and distant metastasis were investigated. The estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status of primary tumor and corresponding metastases were assessed. Tumor phenotype according to receptor status was classified as triple-negative phenotype (TNP) or non-TNP. Concordance and discordance was determined by whether there was a change in receptor status or phenotype between primary and metastatic lesions. Results The rates of discordance between primary breast cancer and metastatic lesions were 18.1%, 25.0%, and 10.3% for ER, PR, and HER2, respectively. The rates of concordant non-TNP, concordant TNP and discordant TNP were 65.9%, 20.9%, and 13.2%, respectively. Patients with concordant ER/PR-negative status had worse postrecurrence survival (PRS) than patients with concordant ER/PR-positive and discordant ER/PR status (p=0.001 and p=0.021, respectively). Patients who converted from HER2-positive to negative after distant metastasis had worst PRS (p=0.040). Multivariate analysis showed that concordant TNP was statistically significant factor for worse PRS (p<0.001). Conclusion Discordance in receptor status and tumor phenotype between primary breast cancer and corresponding metastatic lesions was observed. Patients with concordant TNP had worse long-term outcomes than patients with concordant non-TNP and discordant TNP between primary and metastatic breast cancer. Identifying the receptor status of metastatic lesions may lead to improvements in patient management and survival.

The treatment outcomes and the use of adjuvant therapies in breast cancer patients with severe co-morbidities

Purpose Studies have suggested a potential role of patient’s co-morbidity in determining the survival outcomes of breast cancer. In this study, we examined the long-term oncologic outcomes in breast cancer patients who underwent curative surgery according to their pre-existing comorbid conditions and analyzed the association between the co-morbidity and the use of adjuvant therapies. Methods The medical records of 2,501 patients who underwent surgery for primary breast cancer from June 2006 to June 2010 were reviewed retrospectively. The patients were classified into three groups according to preoperative ASA status determined by the anesthesiologists. Clinico-pathologic characteristics and survival outcomes of the patients were compared among the different co-morbidity groups. Results There were 1,792 (71.6%), 665 (26.6%), and 44 (1.8%) patients in ASA I, II, and III, respectively. Total 95 (3.8%) deaths and 269 (10.8%) recurrences (loco-regional and distant) occurred during the median follow-up period of 71 months. Patients with high comorbidity showed significantly higher rate of deaths (51 (2.8%), 38 (5.7%) and 6 (13.6%) deaths in ASA I, II and III group, respectively, p<0.001). The ASA 3 patients also showed significantly higher rate of breast cancer recurrence when compared to other groups (180 (10.0%), 80 (12.0%) and 9 (20.5%) in ASA I, II, and III, respectively, p = 0.041). Significantly fewer patients in the high co-morbidity group received adjuvant therapies (77 (4.3%), 44 (6.6%) and 8 (18.2%) in ASA I, II, and III, respectively, p<0.001). The increased recurrence of breast cancer in the high morbidity group was mostly seen in patients who did not receive adjuvant therapies. The incidence of serious adverse effect during the adjuvant therapy did not differ according to the co-morbidity conditions. Conclusions In this study, high comorbidity was related to increased risk of death and recurrence in breast cancer. The increased risk of recurrence in high co-morbidity group was mostly seen in patients who did not receive adjuvant therapies. Considering the relatively low rates of serious adverse effects in high co-morbidity patients who received adjuvant therapies, active use of adjuvant therapies in selected patients may improve survival outcomes in breast cancer patients with severe co-morbidities.

An objective nodal staging system for breast cancer patients undergoing neoadjuvant systemic treatment

BackgroundIn this study, we aimed to develop an objective staging system to determine the degree of nodal metastasis in breast cancer patients undergoing neoadjuvant systemic treatment (NST).MethodsWe reviewed the pretreatment computed tomography (CT) images of 392 breast cancer patients who received NST. The association between the patterns of the enlarged regional lymph nodes and treatment outcome was analyzed.ResultsIn the development cohort of 260 patients, 88 (33.8%) patients experienced tumor recurrence and had a significantly higher number of enlarged lymph nodes on the pretreatment CT compared to patients with no recurrence. When patients were classified according to the numbers and locations of enlarged lymph nodes on pretreatment CT, the number of lymph nodes larger than 1 cm was most significantly associated with tumor recurrence. The accuracy of the CT-based nodal staging system was validated in an independent cohort of 132 patients. The presence of the enlarged supraclavicular nodes was associated with worse outcome, but the effect seemed to originate from the accompanied extensive axillary nodal burden. The prognostic effect of the objectively measured axillary nodal metastasis was more pronounced in hormone receptor-negative tumors.ConclusionsWe have developed and validated an objective method of nodal staging in breast cancer patients who undergo NST based on the number of enlarged axillary lymph nodes. Our system can improve the current subjective approach, which uses physical examination alone.

Relapse of Biphenotypic Acute Leukemia as a Breast Mass

In acute leukemia, leukemic infiltration of the breast is extremely rare. We report a case of biphenotypic acute leukemia (BAL) that presented as a breast mass. A 30-year-old woman presented with a 4-month history of a right breast mass with nipple discharge and easy fatigue. She had received chemotherapy and peripheral blood stem cell transplantation for BAL and had been in complete remission for the last 2 years. Core needle biopsy of the breast mass revealed monomorphous infiltrates of blast cells with round nuclei and fine chromatin, consistent with leukemic infiltration. Subsequent bone marrow biopsy showed diffuse infiltration of immature cells. However, bone marrow karyotyping showed 46, XY, suggesting complete engraftment of transplanted donor cells. This is the report of BAL recurring as a breast mass. In the differential diagnosis of a breast mass, extramedullary relapse should be considered when the patient has a history of leukemia.