Impact of 21-Gene Recurrence Score on Chemotherapy Decision in Invasive Ductal Carcinoma of Breast with Nodal Micrometastases / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to investigate the effect of 21-gene recurrence score (RS) on predicting prognosis and chemotherapy decision in node micrometastases (N1mi) breast invasive ductal carcinoma (IDC). MATERIALS AND METHODS: Patients with stage T1-2N1mi and estrogen receptor-positive IDC diagnosed between 2004 and 2015 were included. The associations of 21-gene RS with breast cancer-specific survival (BCSS), chemotherapy decision, and benefit of chemotherapy were analyzed. RESULTS: We identified 4,758 patients including 1,403 patients (29.5%) treated with adjuvant chemotherapy. In the traditional RS cutoffs, 2,831 (59.5%), 1,634 (34.3%), and 293 (6.2%) patients were in the low-, intermediate-, and high-risk RS groups, respectively. In 3,853 patients with human epidermal growth factor receptor-2 (HER2) status available, most patients were HER2-negative disease (98.3%). A higher RS was independently related to chemotherapy receipt, and 14.0%, 47.7%, and 77.8% of patients in the low-, intermediate-, and high-risk RS groups received chemotherapy, respectively. The multivariate analysis indicated that a higher RS was related to worse BCSS (p < 0.001). The 5-year BCSS rates were 99.3%, 97.4%, and 91.9% in patients with low-, intermediate-, and high-risk RS groups, respectively (p < 0.001). However, chemotherapy receipt did not correlate with better BCSS in low-, intermediate-, or high-risk RS groups. There were similar trends using Trial Assigning Individualized Options for Treatment RS cutoffs. CONCLUSION: The 21-gene RS does predict outcome and impact on chemotherapy decision of N1mi breast IDC. Large cohort and long-term outcomes studies are needed to identify the effects of chemotherapy in N1mi patients by different 21-gene RS groups.

KIF11 Functions as an Oncogene and Is Associated with Poor Outcomes from Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The study aimed to search and identify genes that were differentially expressed in breast cancer, and their roles in cancer growth and progression. MATERIALS AND METHODS: The Gene Expression Omnibus (Oncomine) and The Cancer Genome Atlas databases (https://cancergenome.nih.gov/) were screened for genes that were expressed differentially in breast cancer and were closely related to a poor prognosis. Gene expressions were verified by quantitative real-time polymerase chain reaction, and genes were knocked down by a lentivirus-based system. Cell growth and motility were evaluated and in vivo nude mice were used to confirm the in vitro roles of genes. Markers of epithelial-to-mesenchymal transition and the associations of KIF11 with the classical cancer signaling pathways were detected by Western blot. RESULTS: A series of genes expressed differentially in patients with breast cancer. The prognosis associated with high KIF11 expression was poor, and the expression of KIF11 increased significantly in high stage and malignant tumor cells. Inhibiting KIF11 expression in lentivirus-suppressed cells revealed that KIF11 inhibition significantly reduced cell viability and colony formation, inhibited migration and invasion, but promoted apoptosis. The sizes and weights of KIF11-inhibited tumors in nude mice were significantly lower than in the negative controls. Western blot showed that E-cadherin in breast cancer was significantly upregulated in KIF-inhibited cells and tumor tissues, whereas N-cadherin and vimentin were significantly down-regulated. BT549 and MDA231 cells with KIF11 knockdown exhibited decreased ERK, AMPK, AKT, and CREB phosphorylation. CONCLUSION: KIF11 acts as a potential oncogene that regulates the development and progression of breast cancer.

Early-stage node negative cervical adenocarcinoma and squamous cell carcinoma show similar survival outcomes after hysterectomy: a population-based study / 부인종양

OBJECTIVE: To investigate the clinicopathological features and outcomes between node-negative, early-stage cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC) after hysterectomy. METHODS: Patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stages I–IIA cervical SCC and AC between 1988 and 2013 were retrospectively reviewed using the Surveillance, Epidemiology, and End Results database. We used propensity score-matching to balance patient baseline characteristics. Univariate and multivariate Cox regression analyses were used for prognostic analyses of cause-specific survival (CSS) and overall survival (OS). RESULTS: A total of 9,858 patients were identified, comprising 6,117 patients (62.1%) and 3,741 (37.9%) patients with cervical SCC and AC, respectively. Compared with cervical SCC, cervical AC cases were more likely to be younger, diagnosed after 2000, white, and have well-differentiated and FIGO stage IB1 disease. For SCC and AC, the 10-year CSS rates were 93.4% and 94.7%, respectively (p=0.011), and the 10-year OS rates were 89.6% and 92.2%, respectively (p<0.001). Multivariate analysis revealed that age, ethnicity, tumor grade, and FIGO stage were independent prognostic factors of CSS and OS, but that histologic subtype was not associated with CSS and OS. In the propensity score-matched patient population, univariate and multivariate analyses also showed that histologic subtype was not associated with survival outcomes. CONCLUSION: Cervical AC has equivalent survival to cervical SCC in node-negative, early-stage disease after hysterectomy and lymphadenectomy.

Using the Lymph Node Ratio to Evaluate the Prognosis of Stage II/III Breast Cancer Patients Who Received Neoadjuvant Chemotherapy and Mastectomy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was conducted to investigate the prognostic value of lymph node ratio (LNR) in stage II/III breast cancer patients who undergo mastectomy after neoadjuvant chemotherapy. MATERIALS AND METHODS: Clinical and pathological data describing stage II/III breast cancer patients were included in this retrospective study. The primary outcomes were locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). RESULTS: Among 277 patients, there were 43 ypN0, 64 ypN1, 89 ypN2, and 81 ypN3 cases. Additionally, there were 43, 57, 92 and 85 cases in the LNR 0, 0.01-0.20, 0.21-0.65, and > 0.65 groups, respectively. The median follow-up was 49.5 months. Univariate analysis showed that both ypN stage and LNR were prognostic factors of LRFS, DMFS, DFS, and OS (p 0.05). CONCLUSION: The integrated use of LNR and ypN may be suitable for evaluation the prognosis of stage II/III breast cancer patients who undergo mastectomy after neoadjuvant chemotherapy.

Ovarian Ablation Using Goserelin Improves Survival of Premenopausal Patients with Stage II/III Hormone Receptor-Positive Breast Cancer without Chemotherapy-Induced Amenorrhea / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to assess the value of ovarian ablation using goserelin in premenopausal patients with stage II/III hormone receptor-positive breast cancer without chemotherapy-induced amenorrhea (CIA). MATERIALS AND METHODS: We retrospectively reviewed the data of breast patients treated between October 1999 and November 2007 without CIA. The Kaplan-Meier method was used for calculation of the survival rate. Log rank method and Cox regression analysis were used for univariate and multivariate prognostic analysis. RESULTS: The median follow-up period was 61 months. Initially, 353 patients remained without CIA after chemotherapy and 98 among those who received goserelin and tamoxifen (TAM). In univariate analysis, goserelin improved locoregional recurrence-free survival (LRFS) (98.9% vs. 94.1%, p=0.041), distant metastasis-free survival (DMFS) (85.4% vs. 71.9%, p=0.006), disease-free survival (DFS) (85.4% vs. 71.6%, p=0.005), and overall survival (OS) (93.5% vs. 83.5%, p=0.010). In multivariate analysis, goserelin treatment was an independent factor influencing DMFS (hazard ratio [HR], 1.603; 95% confidence interval [CI], 1.228 to 2.092; p=0.001), DFS (HR, 1.606; 95% CI, 1.231 to 2.096; p=0.001), and OS (HR, 3.311; 95% CI, 1.416 to 7.742; p=0.006). In addition, treatment with goserelin resulted in significantly improved LRFS (p=0.039), DMFS (p=0.043), DFS (p=0.036), and OS (p=0.010) in patients aged or = 40 years, goserelin only improved DMFS (p=0.028) and DFS (p=0.027). CONCLUSION: Ovarian ablation with goserelin plus TAM resulted in significantly improved therapeutic efficacy in premenopausal patients with stage II/III hormone receptor-positive breast cancer without CIA.

Feasibility and acute toxicity of 3-dimensional conformal external-beam accelerated partial-breast irradiation for early-stage breast cancer after breast-conserving surgery in Chinese female patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A growing number of studies worldwide have advocated the replacement of whole-breast irradiation with accelerated partial breast irradiation using three-dimensional conformal external-beam radiation (APBI-3DCRT) for early-stage breast cancer. But APBI can be only used in selected population of patients with early-staged breast cancer. It is not replacing the whole breast radiotherapy. This study aimed to examine the feasibility and acute normal tissue toxicity of the APBI-3DCRT technique in Chinese female patients who generally have smaller breasts compared to their Western counterparts.</p><p><b>METHODS</b>From May 2006 to December 2009, a total of 48 Chinese female patients (with early-stage breast cancer who met the inclusion criteria) received APBI-3DCRT after breast-conserving surgery at Sun Yat-sen University Cancer Center. The total dosage from APBI-3DCRT was 34 Gy, delivered in 3.4 Gy per fractions, twice per day at intervals of at least six hours. The radiation dose, volume of the target area and volume of irradiated normal tissues were calculated. Acute toxicity was evaluated according to the Common Toxicity Criteria (CTC) 3.0.</p><p><b>RESULTS</b>Among the 48 patients, the planning target volume for evaluation (PTVE) was (90.42 ± 9.26) cm³, the ipsilateral breast volume (IBV) was (421.74 ± 28.53) cm³, and the ratio between the two was (20.74 ± 5.86)%. Evaluation of the dosimetric characteristics of the PTVE revealed excellent dosimetric results in 14 patients and acceptable results in 34 patients. The dose delivered to the PTVE ranged from 93% to 110% of the prescribed dose. The average ratio of the volume of PTVE receiving 95% of the prescription dose (V95) was (99.26 ± 0.37)%. The habituation index (HI) and the conformity index (CI) were 1.08 ± 0.01 and 0.72 ± 0.02, respectively, suggesting good homogeneity and conformity of the dose delivered to the target field. The radiation dose to normal tissues and organs was within the dose limitation. Subjects experienced mild acute toxicity. The main manifestations were breast edema in 22 patients, breast pain in 7, skin erythema in 25, general malaise in 22 and cytopenia in 8. No acute radiological cardiac or pulmonary injury was found.</p><p><b>CONCLUSIONS</b>The results of our short-term follow-up showed that it is feasible to perform APBI-3DCRT for early-stage breast cancer after breast-conserving surgery in Chinese female patients with smaller breasts. However, further studies are required to elucidate its efficacy and long-term side effects.</p>

Dosimetry of electron-beam chest-wall irradiation after mastectomy in patients with left breast cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the dosimetric advantages of postmastectomy electron-beam chest-wall irradiation after left mastectomy in patients with breast cancer.</p><p><b>METHODS</b>Electron-beam chest-wall irradiation and tangential field irradiation were planned using Pinnacle7.4f planning systems for 42 patients with left breast cancer after mastectomy. The total prescribed dose for both plans was 5000 cGy/25 fractions. The dose volume histogram was used to compare the dosimetry of the clinical target volume (CTV) and the organs at risk such as the heart and ipsilateral lung.</p><p><b>RESULTS</b>The maximum dose (Dmax) of the CTV of electron beam chest-wall irradiation plans was significantly higher than that of tangential field irradiation plans (5562±61 vs 5402±82 cGy, t=6.10, P<0.05). The CTV of the electron beam chest-wall irradiation plans showed better heterogeneity than that of the tangential field irradiation plans, with heterogeneity index of 1.18±0.03 and 1.13±0.18, respectively (t=6.50, P<0.05). Electron beam chest-wall irradiation plans had also a better conformal index of the CTV than tangential field irradiation plans (0.77±0.17 vs 0.57±0.17, t=3.49, P<0.05). The V40 of the ipsilateral lung, the maximum dose of the heart, V30 and V40 of the heart in the electron beam chest-wall irradiation plans were smaller than those of the tangential field irradiation plans [(5.86±3.68)% vs (8.73±3.26)%, t=-2.27, P<0.05; 4839±388 cGy vs 5095±176 cGy, t=-2.32, P<0.05; (2.58±1.50)% vs (7.20±2.62)%, t=-4.70, P<0.05; (1.74±1.23)% vs (4.20±2.51)%, t=-3.50, P<0.05].</p><p><b>CONCLUSION</b>Compared with the tangential field irradiation plans, electron-beam chest-wall irradiation has better coverage index of the CTV and can decrease the high-dose volume of the normal tissue, but shows a poorer habituation index of the CTV.</p>

The clinical value of adjuvant radiotherapy in patients with early stage breast cancer with 1 to 3 positive lymph nodes after mastectomy / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>The role of postmastectomy radiotherapy (PMRT) in breast cancer patients with T1-T2 tumors and 1-3 positive axillary nodes is still uncertain. This study investigated the value of PMRT for these patients.</p><p><b>METHODS</b>In the retrospective data of 488 eligible patients, survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using a log-rank test and the Cox proportional hazards model, respectively.</p><p><b>RESULTS</b>The median observation time was 54 months. The 5- and 10-year locoregional recurrence-free survival (LRFS) rates were 90.8% and 86.9%, respectively. The 5- and 10-year disease-free survival (DFS) rates were 82.0% and 74.3%, respectively. The 5- and 10-year overall survival (OS) rates were 90.7% and 82.7%, respectively. For the 412 patients without PMRT, T2 classification, 2-3 positive nodes, and hormone (estrogen and progesterone) receptor-negative were risk factors for locoregional recurrence in the multivariate analysis. On the basis of these 3 risk factors, the group with 2-3 factors had a 10-year LRFS rate of 63.1% compared with 96.1% for the group with 0-1 factors (P < 0.001). For the group with 2-3 risk factors, LRFS and DFS were significantly improved by PMRT, with the 5- and 10-year LRFS rates without PMRT of 82.4% and 63.1%, respectively, and, with PMRT, of 98.1% at both 5 years and 10 years (P = 0.002). The 5- and 10-year DFS rates without PMRT were 72.0% and 57.6%, respectively, and, with PMRT, the 5- and 10-year DFS rates were 89.4% and 81.7%, respectively (P = 0.007). There was no significant difference in the 10-year OS rates between patients with and without PMRT. However, there is the potential benefit of 15.3% (87.1% vs. 71.8%, P = 0.072). Conversely, the group with 0-1 factors of PMRT had no effect on prognosis.</p><p><b>CONCLUSIONS</b>In patients receiving mastectomy with T1-T2 breast cancer with 1-3 positive nodes, for the group with 2-3 risk factors, PMRT significantly improved LRFS and DFS and has potential benefit in OS.</p>