PURPOSE: A growing body of evidence indicates that zoledronic acid (ZA) can improve the clinical outcome in patients with breast cancer and low estrogen levels. In the present study, we aimed to investigate the survival benefit of ZA administration in postmenopausal Korean women with breast cancer who were also receiving aromatase inhibitors. METHODS: Between January 2004 and December 2010, 235 postmenopausal breast cancer patients undergoing aromatase inhibitor therapy were investigated. All patients were postmenopausal, as confirmed by laboratory tests. Of these patients, 77 received adjuvant upfront ZA for at least 1 year in addition to conventional adjuvant treatment. The remaining 158 patients never received ZA and were treated according to the St. Gallen guidelines. RESULTS: The baseline characteristics for ZA treatment were not different between the two groups. The median follow-up time was 62 months, and the patients who received ZA in addition to aromatase inhibitors showed a better recurrence-free survival compared to those who received aromatase inhibitors alone (p=0.035). On multivariate analysis, the patients who received ZA showed a better recurrence-free survival independent of the tumor size, nodal status, progesterone receptor, and histological grade. For this model, Harrell c index was 0.743. The hazard ratio of ZA use for recurrence-free survival was 0.12 (95% confidence interval, 0.01-0.99). CONCLUSION: Our findings suggest that upfront use of ZA as part of adjuvant treatment can offer a survival benefit to postmenopausal breast cancer patients receiving aromatase inhibitor treatment.
Aromatase ; Aromatase Inhibitors* ; Breast Neoplasms* ; Estrogens ; Female ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Postmenopause ; Receptors, Progesterone

With the advance in personalized therapeutic strategies in patients with breast cancer, there is an increasing need for biomarker-guided therapy. Although the immunogenicity of breast cancer has not been strongly considered in research or practice, tumor-infiltrating lymphocytes (TILs) are emerging as biomarkers mediating tumor response to treatments. Earlier studies have provided evidence that the level of TILs has prognostic value and the potential for predictive value, particularly in triple-negative and human epidermal growth factor receptor 2-positive breast cancer. Moreover, the level of TILs has been associated with treatment outcome in patients undergoing neoadjuvant chemotherapy. To date, no standardized methodology for measuring TILs has been established. In this article, we review current issues and clinical evidence for the use of TILs in breast cancer.
Biomarkers ; Breast Neoplasms* ; Breast* ; Drug Therapy ; Humans ; Immune System ; Lymphocytes, Tumor-Infiltrating* ; Negotiating ; Receptor, Epidermal Growth Factor ; Treatment Outcome ; Triple Negative Breast Neoplasms

Tumor heterogeneity of triple-negative breast cancer (TNBC) has been the main barrier in conquering breast cancer. To dissect the molecular diversity of TNBC and discover therapeutic targets for TNBC, the molecular classification of TNBC is a prioritized issue in research area. Accordingly, recent studies have been successful in classifying TNBC into several distinct subtypes with specific biologic pathways. Despite the different methodologies used and varied number of final subtypes, these studies identically suggested that TNBC consists of four major subtypes: basal-like, mesenchymal, luminal androgen receptor, and immune-enriched. By reviewing these methods of classifications of TNBC, we highlight the unmet need to develop a molecular classifier suited for TNBC.
Breast Neoplasms ; Classification* ; Gene Expression ; Phenobarbital ; Population Characteristics ; Receptors, Androgen ; Triple Negative Breast Neoplasms*

PURPOSE: The prognosis of breast cancer has been consistently improving. We analyzed our cohort of breast cancer patients with a long-term follow up at a single center over time. MATERIALS AND METHODS: A total of 1889 patients with known cancer stages were recruited and analyzed between January 1991 and December 2005. Patients were classified according to the time periods (1991-1995; 1996-2000; 2001-2005). To determine intrinsic subtypes, 858 patients whose human epidermal growth receptor-2 status and Ki67 were reported between April 2004 and December 2008 were also analyzed. RESULTS: At a median follow up of 9.1 years, the 10-year overall survival (OS) rate was 80.5% for the entire cohort. On multivariate analysis for OS and recurrence-free survival (RFS), the time period was demonstrated to be a significant factor independent of conventional prognostic markers. In the survival analysis performed for each stage (I to III), OS and RFS significantly improved according to the time periods. Adoption of new agents in adjuvant chemotherapy and endocrine therapy was increased according to the elapsed time. In the patients with known subtypes, OS and RFS significantly differed among the subtypes, and the triple-negative subtype showed the worst outcome in stages II and III. CONCLUSION: In the Korean breast cancer cohort with a long-term follow up, our data show an improved prognosis over the past decades, and harbor the contribution of advances in adjuvant treatment. Moreover, we provided new insight regarding comparison of the prognostic impact between the tumor burden and subtypes.
Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/*epidemiology/pathology ; *Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Multivariate Analysis ; Prognosis ; Republic of Korea ; Survival Analysis ; Survival Rate ; Time Factors

PURPOSE: Tumor response to neoadjuvant chemotherapy (NAC) may adversely affect the identification and accuracy rate of sentinel lymph node biopsy (SLNB). This study was conducted to evaluate the feasibility of SLNB in node-positive breast cancer patients with negative axillary conversion after NAC. MATERIALS AND METHODS: Ninety-six patients with positive nodes at presentation were prospectively enrolled. 18Fluorodeoxyglucose-positron emission tomography (18F-FDG PET) and ultrasonography were performed before and after NAC. A metastatic axillary lymph node was defined as positive if it was positive upon both 18F-FDG PET and ultrasonography, while it was considered negative if it was negative upon both 18F-FDG PET and ultrasonography. RESULTS: After NAC, 55 cases (57.3%) became clinically node-negative, while 41 cases (42.7%) remained node-positive. In the entire cohort, the sentinel lymph node (SLN) identification and false-negative rates were 84.3% (81/96) and 18.4% (9/49), respectively. In the negative axillary conversion group, the results of SLNB showed an 85.7% (48/55) identification rate and 16.7% (4/24) false-negative rate. CONCLUSION: For breast cancer patients with clinically positive nodes at presentation, it is difficult to conclude whether the SLN accurately represents the metastatic status of all axillary lymph nodes, even after clinically negative node conversion following NAC.
Breast Neoplasms* ; Cohort Studies ; Drug Therapy* ; Fluorodeoxyglucose F18 ; Humans ; Lymph Nodes ; Neoadjuvant Therapy ; Predictive Value of Tests ; Prospective Studies* ; Sentinel Lymph Node Biopsy* ; Ultrasonography

Purpose: Adherence and persistence to adjuvant hormone therapy (AHT) are seldom maintained among early-stage hormone receptor-positive breast cancer (BC) survivors, despite the significant clinical benefits of long-term AHT. As the factors influencing adherence to AHT remain unclear, this study aimed to comprehensively identify such factors and classify them into specific dimensions. Methods: PubMed, Cochrane Library, Embase, PsycINFO, and CINAHL were searched for qualified articles. The search mainly focused on three components: early-stage (0–III) BC, oral AHT administration, and adherence to AHT, with keywords derived from MeSH and entry terms. The factors identified were then classified into six categories based on a modified WHO multidimensional model. Results: Overall, 146 studies were included; the median sample size was 651 (range, 31– 40,009), and the mean age of the population was 61.5 years (standard deviation, 8.3 years).Patient- and therapy-related factors were the most frequently investigated factors. Necessity/ concern beliefs and self-efficacy among patient-related factors were consistently related to better adherence than depression. Although drug side effects and medication use cannot be modified easily, a refined prescription strategy for the initiation and switching of AHT is likely to increase adherence levels. Conclusion An effective psychological program that encourages positive views and beliefs about medication and management strategies for each therapy may be necessary to improve adherence to AHT. Social support and a sense of belonging can be enhanced through community participation and social media for better adherence to AHT. Patient-centered communication and appropriate recommendations by physicians may be attributable to better adherence outcomes. Findings from systematically organized factors that influence adherence to AHT may contribute to the establishment of intervention strategies to benefit patients with early-stage BC to achieve optimal health.

PURPOSE: Breast cancer is heterogeneous disease and the response to chemotherapeutic agents is also heterogeneous from patient to patient. Chemotherapy response assay is in vitro test that is performed to evaluate the degree of tumor growth inhibition by chemotherapy drugs. In this study, we performed the chemotherapy response assay using adenosine triphosphate (ATP-CRA) in breast cancer patients and assessed the clinical availability. METHODS: Sixty five breast cancer patients were enrolled in this study. Cancer cells were evenly divided and treated with commonly used chemotherapeutic drugs in breast cancer (doxorubicin, epirubicin, 5-fluorouracil, paclitaxel, docetaxel, vinorelbine, and gemcitabine). To verify in vitro ATP-CRA indirectly, we analyzed the correlation between cell death rate (CDR) of doxorubicin and epirubicin, and between doxorubicin and paclitaxel. We also analyzed the mean CDR of doxorubicin, epirubicin and paclitaxel by HER2 status. RESULTS: We could successfully perform the ATP-CRA in 60 patients (95.2%). In all cases, we can get the results within 7 days. The range of CDR was very wide, from 0 to more than 50%, except gemcitabine. Epirubicin showed the highest mean CDR (39.9%) and doxorubicin, paclitaxel in order. According to the chemosensitivity index, paclitaxel is the most frequently first-ranked and doxorubicin, epirubicin in order. Correlation coefficient between the cell death rate of doxorubicin and epirubicin is 0.4210 and 0.1299 between paclitaxel and doxorubicin. In HER2 positive group, mean CDR of paclitaxel, epirubicin and doxorubicin was higher than in HER2 negative group, even though epirubicin and doxorubicin were not statistically significant (p=0.018, p=0.114, p=0.311, respectively). CONCLUSION: ATP-CRA showed heterogeneous results in individual patients. ATP-CRA was successful and can be performed within short time period. According to our in vitro study, it showed similar results with in vivo study but for the clinical use, the prospective randomized controlled trial should be preceded.
Adenosine Triphosphate ; Breast ; Breast Neoplasms ; Cell Death ; Deoxycytidine ; Doxorubicin ; Epirubicin ; Fluorouracil ; Humans ; Paclitaxel ; Polyphosphates ; Taxoids ; Vinblastine

PURPOSE: To report the results of a correlation analysis of skin dose assessed by in vivo dosimetry and the incidence of acute toxicity. This is a phase 2 trial evaluating the feasibility of intraoperative radiotherapy (IORT) as a boost for breast cancer patients. MATERIALS AND METHODS: Eligible patients were treated with IORT of 20 Gy followed by whole breast irradiation (WBI) of 46 Gy. A total of 55 patients with a minimum follow-up of 1 month after WBI were evaluated. Optically stimulated luminescence dosimeter (OSLD) detected radiation dose delivered to the skin during IORT. Acute toxicity was recorded according to the Common Terminology Criteria for Adverse Events v4.0. Clinical parameters were correlated with seroma formation and maximum skin dose. RESULTS: Median follow-up after IORT was 25.9 weeks (range, 12.7 to 50.3 weeks). Prior to WBI, only one patient developed acute toxicity. Following WBI, 30 patients experienced grade 1 skin toxicity and three patients had grade 2 skin toxicity. Skin dose during IORT exceeded 5 Gy in two patients: with grade 2 complications around the surgical scar in one patient who received 8.42 Gy. Breast volume on preoperative images (p = 0.001), ratio of applicator diameter and breast volume (p = 0.002), and distance between skin and tumor (p = 0.003) showed significant correlations with maximum skin dose. CONCLUSIONS: IORT as a boost was well-tolerated among Korean women without severe acute complication. In vivo dosimetry with OSLD can help ensure safe delivery of IORT as a boost.
Breast Neoplasms* ; Breast* ; Cicatrix ; Female ; Follow-Up Studies ; Humans ; Incidence ; Luminescence ; Mastectomy, Segmental ; Radiotherapy* ; Seroma ; Skin

PURPOSE: We investigated the relationships between metastasis-free interval (MFI) and tumor characteristics, and assessed the prognostic value of MFI for survival after metastasis in patients with metastatic breast cancer. Furthermore, we compared MFI among the subtypes. METHODS: We identified 335 patients with postoperative tumor recurrence at distant site(s). All patients underwent curative resection and had a MFI of at least 6 months. MFI was categorized as short (<2 years), intermediate (> or =2 years and <5 years), or long (> or =5 years). Overall survival after metastasis (OSM) was estimated. RESULTS: Patients with a shorter MFI were younger, more likely to have initial metastasis to visceral organs, and had a larger tumor with a higher stage and grade as well as a higher rate of nodal involvement at initial diagnosis. Among 136 patients with known disease subtypes, shorter MFI was associated with the triple-negative subtype while longer MFI was associated with the hormone receptor-positive/human epidermal growth factor receptor 2 negative subtype. Mortality after metastasis declined sharply with increasing MFI up to approximately 2 years, and continued gradually declining between 2 and 5 years. An MFI longer than 5 years did not add any survival benefit. MFI was a significant prognostic factor for OSM independent of nodal status, stage, metastatic site, and hormone receptor status of the metastasized cancer. CONCLUSION: MFI is closely related to biological characteristics of both primary tumors and their metastases, and has a prognostic value for survival after metastasis. We therefore suggest investigation into treatments targeting improvement of MFI as a potential novel strategy.
Breast Neoplasms* ; Breast* ; Diagnosis ; Humans ; Mortality ; Neoplasm Metastasis ; Population Characteristics ; Receptor, Epidermal Growth Factor ; Recurrence*

PURPOSE: Bone is the most frequent site of metastasis among breast cancer patients. We investigated prognostic factors affecting survival following bone-only metastasis in breast cancer patients. MATERIALS AND METHODS: The medical records of breast cancer patients who were treated and followed at Gangnam Severance Hospital retrospectively reviewed to identify patients with bone-only metastasis. RESULTS: The median time from the diagnosis of bone-only metastasis to the last follow-up or death was 55.2 [95% confidence interval (CI), 38.6-71.9] months. The Kaplan-Meier overall survival estimate at 10 years for all patients was 34.9%. In the multivariate Cox regression model, bisphosphonate treatment [hazard ratio=0.18; 95% CI, 0.07-0.43], estrogen receptor positivity (hazard ratio=0.51; 95% CI, 0.28-0.94), and solitary bone metastasis (hazard ratio=0.32; 95% CI, 0.14-0.72) were significantly associated with longer overall survival in the bone-only recurrence group. Among the treatment modalities, only bisphosphonate treatment was identified as a significant prognostic factor. CONCLUSION: Identifying the factors influencing breast cancer mortality after bone-only metastasis will help clarify the clinical course and improve the treatment outcome for patients with breast cancer and bone-only metastasis. Bisphosphonates, as a significant prognostic factor, warrant further investigation.
Adult ; Antineoplastic Agents/therapeutic use ; Bone Neoplasms/drug therapy/genetics/*secondary ; Breast Neoplasms/drug therapy/genetics/*pathology ; Female ; Humans ; Middle Aged ; Multivariate Analysis ; Prognosis ; Receptors, Estrogen/genetics ; Receptors, Progesterone/genetics ; Regression Analysis ; Retrospective Studies ; Survival Analysis