Soo Kyung Ahn

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.

Breast cancer molecular phenotype and the use of HER2-targeted agents influence the accuracy of breast MRI after neoadjuvant chemotherapy.

Objective:To investigate whether the accuracy of magnetic resonance imaging (MRI) after neoadjuvant systemic therapy (NST) is affected by molecular features of primary breast cancer and the use of human epidermal growth factor receptor 2 (HER2)-targeted agents. Background:Improved understanding of factors affecting the accuracy of breast MRI after NST can lead to more tailored use of MRI in deciding surgical extent after NST. Methods:We analyzed the imaging and clinicopathological data of 463 patients who underwent NST. We aimed to investigate whether the molecular subtypes, and the use of targeted therapies, were associated with changes in the accuracy of MRI predicting residual tumor extent. Results:The accuracy of MRI predicting the residual tumor extent was most accurate in triple-negative breast cancer and was least accurate in Luminal A subtype (Pearson correlation coefficient of 0.754 and 0.531, respectively). Multivariate analysis suggested estrogen receptor (ER) status as an independent factor influencing the MRI accuracy. In HER2-amplified tumors, the use of HER2-targeted agents was associated with a less accurate MRI prediction. Conclusions:The accuracy of MRI in predicting residual tumor extent was lowest in ER-positive tumors treated with NST. In HER2-positive tumors, the use of HER2-targeted agents resulted in a less accurate MRI after NST. These factors should be considered for deciding the extent of breast conservation after neoadjuvant chemotherapy.

Predictive Significance of p53, Ki-67, and Bcl-2 Expression for Pathologic Complete Response after Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer

Purpose Patients with triple-negative breast cancer (TNBC) with pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) have superior survival outcomes compared to those with residual disease after NAC. This study investigated the value of three biomarkers, p53, Ki-67, and Bcl-2 for predicting pCR in NAC-treated patients with TNBC. Methods Between 2003 and 2012, 198 patients with pathologically confirmed primary TNBC were treated with two different taxane-based chemotherapeutic regimens prior to surgery. Before NAC, expression of p53 (cutoff 25%), Ki-67 (cutoff 10%), and Bcl-2 (cutoff 10%) was assessed immunohistochemically in core biopsy specimens. The incidence of pCR was correlated with the expression of these biomarkers. Results Overall, pCR occurred in 37 of the 198 patients (18.7%). A significant association was observed between the pCR rate and overexpression of the p53 and Ki-67 biomarkers. Multivariate analysis showed that only p53 expression was independently associated with pCR to NAC (odds ratio, 3.961; p=0.003). The sensitivity, specificity, positive predictive value, and negative predictive value of p53 expression for predicting pCR were 77.8%, 50.3%, 26.2%, and 90.9%, respectively. The pCR rate was the lowest (5.2%) in patients with low expression of both p53 and Ki-67, and it was the highest (25.8%) when both biomarkers showed high expression. Conclusion Expression of p53 was significantly associated with pCR after NAC in patients with TNBC, suggesting that this biomarker might be particularly valuable in identifying TNBC patients prone to have residual disease after NAC.

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.

Prognostic effect of preoperative serum estradiol level in postmenopausal breast cancer

BackgroundThe prognostic role of serum estrogen level in breast cancer patients is unclear. We investigated the prognostic importance of preoperative serum estradiol (E2) level in postmenopausal women according to their estrogen receptor (ER) status.MethodsThe medical records of 313 postmenopausal breast cancer patients who underwent surgery between 2006 and 2008 at a single institution were retrospectively evaluated. Patients who received neoadjuvant chemotherapy, synchronous bilateral breast cancer, or those with metastasis at diagnosis were excluded. Serum E2 and follicular stimulating hormone (FSH) levels were measured by radioimmunoassay and immunoradiometric assay, respectively, within 3 months prior to surgery. After a median follow-up of 52.0 months (11–77 months), 21 women were found to have metastatic disease.ResultsThe overall, median E2 level was 13.0 pg/ml, and was slightly higher in ER-positive than ER-negative (p=0.69). The mean serum E2 level was significantly higher in patients with metastasis (17.41±8.34 pg/ml) than in those without metastasis (13.54±7.58 pg/ml) (p=0.02). Kaplan-Meier analysis using a cut-off of 13 pg/ml showed that, ER negative (p=0.02) but not ER positive (p>0.05) patients with higher E2 level showed significantly poorer metastasis-free survival. Multivariate analysis showed that, the high E2 level of ER negative tumors was an independent negative prognostic factor for metastasis- free survival (HR, 3.32; 95% CI, 1.05 to 10.51; p=0.04).ConclusionsHigher preoperative serum E2 level had a negative prognostic effect in postmenopausal women with breast cancer, especially in the ER-negative subgroup.

Validation of a Scoring System for Predicting Malignancy in Patients Diagnosed with Atypical Ductal Hyperplasia Using an Ultrasound-Guided Core Needle Biopsy

Purpose The need for surgical excision in patients with ultrasound-guided core needle biopsy (CNB)-diagnosed atypical ductal hyperplasia (ADH) remains an issue of debate. The present study sought to validate a scoring system (the U score, for underestimation) that we have previously developed for predicting malignancy in CNB-diagnosed ADH. Methods The study prospectively enrolled 85 female patients with CNB-diagnosed ADH who underwent subsequent surgical excision. Underestimation was defined as a surgical specimen having malignant foci. Results The overall underestimation rate was 37% (31/85). Multivariate analysis showed that a clinically palpable mass, microcalcification on imaging, size >15 mm and a patient age of ≥50 years were independently associated with underestimation. When applied to the scoring system, the validation score was significant (p<0.001; area under the curve, 0.852). No patient with a U score <3.5 had an underestimated lesion. Conclusion The present study successfully validated the efficacy of our scoring system for predicting malignancy in CNB-diagnosed ADH. A U score of ≤3.5 indicates that surgical excision may not be necessary.

Grade of ductal carcinoma in situ accompanying infiltrating ductal carcinoma as an independent prognostic factor.

BACKGROUND Several studies about the relationship between IDC and DCIS have been reported, but no consensus has been reached regarding clinical characteristics and prognostic value. PATIENTS AND METHODS We reviewed the medical records of patients who underwent surgery for IDC between 2006 and 2008. DCIS adjacent to IDC was pathologically classified as either high-grade DCIS or non-high-grade DCIS. RESULTS Among 1751 IDC patients within the study period, 1384 patients (79.0%) had concomitant DCIS. There was no survival difference between patients with pure IDC and those with IDC and concomitant DCIS. However, patients with high-grade DCIS had worse survival than did patients with non-high-grade DCIS or pure IDC (5-year recurrence-free survival rates for IDC with non-high-grade DCIS, pure IDC without DCIS, and IDC with high-grade DCIS were 97%, 93%, and 86%, respectively; P = .001). This tendency was maintained regardless of estrogen receptor status or histologic grade of IDC. In a Cox regression model, patients with IDC and accompanying high-grade DCIS had a 2.5-fold higher probability of local or distant relapse than did those with IDC and low-grade DCIS (hazard ratio, 2.51; 95% confidence interval, 1.12-5.64). CONCLUSIONS The prognosis of patients with invasive breast cancer differed according to the grade of concomitant adjacent DCIS. Accordingly, the grade of adjacent DCIS should be considered as a prognostic factor in the clinical management of patients with breast cancer. However, in our study, the follow-up periods were short to confirm prognostic effect. Further studies are needed.

Can We Skip Intraoperative Evaluation of Sentinel Lymph Nodes? Nomogram Predicting Involvement of Three or More Axillary Lymph Nodes before Breast Cancer Surgery

Purpose The American College of Surgeons Oncology Group Z0011 trial reported that complete dissection of axillary lymph nodes (ALNs) may not be warranted in women with clinical T1-T2 tumors and one or two involved ALNs who were undergoing lumpectomy plus radiation followed by systemic therapy. The present study was conducted to identify preoperative imaging predictors of ≥ 3 ALNs. Materials and Methods The training set consisted of 1,917 patients with clinical T1-T2 and node negative invasive breast cancer. Factors associated with ≥ 3 involved ALNs were evaluated by logistic regression analysis. The validation set consisted of 378 independent patients. The nomogram was applied prospectively to 512 patients who met the Z0011 criteria. Results Of the 1,917 patients, 204 (10.6%) had ≥ 3 positive nodes. Multivariate analysis showed that involvement of ≥ 3 nodes was significantly associated with ultrasonographic and chest computed tomography findings of suspicious ALNs (p < 0.001 each). These two imaging criteria, plus patient age, were used to develop a nomogram calculating the probability of involvement of ≥ 3 ALNs. The areas under the receiver operating characteristic curve of the nomogram were 0.852 (95% confidence interval [CI], 0.820 to 0.883) for the training set and 0.896 (95% CI, 0.836 to 0.957) for the validation set. Prospective application of the nomogram showed that 60 of 512 patients (11.7%) had scores above the cut-off. Application of the nomogram reduced operation time and cost, with a very low re-operation rate (1.6%). Conclusion Patients likely to have ≥ 3 positive ALNs could be identified by preoperative imaging. The nomogram was helpful in selective intraoperative examination of sentinel lymph nodes.

Nomogram for Predicting Breast Conservation after Neoadjuvant Chemotherapy

Purpose The ability to accurately predict the likelihood of achieving breast conservation surgery (BCS) after neoadjuvant chemotherapy (NCT) is important in deciding whether NCT or surgery should be the first-line treatment in patients with operable breast cancers. Materials and Methods We reviewed the data of 513 women, who had stage II or III breast cancer and received NCT and surgery from a single institution. The ability of various clinicopathologic factors to predict the achievement of BCS and tumor size reduction to ≤ 3 cm was assessed. Nomograms were built and validated in an independent cohort. Results BCS was performed in 50.1% of patients, with 42.2% of tumors reduced to ≤ 3 cm after NCT. A multivariate logistic regression analysis showed that smaller initial tumor size, longer distance between the lesion and the nipple, absence of suspicious calcifications on mammography, and a single tumor were associated with BCS rather than mastectomy (p < 0.05). Negative estrogen receptor, smaller initial tumor size, higher Ki-67 level, and absence of in situ component were associated with residual tumor size ≤ 3 cm (p < 0.05). Two nomograms were developed using these factors. The areas under the receiver operating characteristic curves for nomograms predicting BCS and residual tumor ≤ 3 cm were 0.800 and 0.777, respectively. The calibration plots showed good agreement between the predicted and actual probabilities. Conclusion We have established a model with novel factors that predicts BCS and residual tumor size after NCT. This model can help in making treatment decisions for patients who are candidates for NCT.