A preliminary report of head-to-head comparison of 18-gene-based clinical-genomic model and oncotype DX 21-gene assay for predicting recurrence of early-stage breast cancer.

BACKGROUND: The information of Oncotype DX applied in Asian breast cancer patients is limited. A recurrence index for distant recurrence (RI-DR) has been developed for early-stage breast cancer (EBC) from tumor samples in Chinese patients. In this study, we compared the prognostic performance of the Oncotype DX (ODx) recurrence score (RS) with the RI-DR for any recurrence risk type. MATERIALS AND METHODS: One hundred thirty-eight (138) patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative EBC who were previously tested with ODx were included for testing with the RI-DR. The cutoff score to partition the low- and high-risk patients was 26 for RS and 36 for RI-DR. The primary endpoint was recurrence-free survival (RFS). RESULTS: The concordance between the RI-DR and RS was 83% in N0 patients and 81% in node-positive patients when the RS score cutoff was set at 26. With a median follow-up interval of 36.8 months, the 4-year RFS for the high- and low-risk groups categorized by the RS were 61.9% and 95.0%, respectively (hazard ratio: 10.6, 95.0% confidence interval [CI]: 1.8-62.9). The 4-year RFS in the high- and low-risk groups categorized by the RI-DR were 72.6% and 98.5%, respectively (hazard ratio: 18.9, 95% CI: 1.8-138.8). CONCLUSION: This paper illustrated the performance of RI-DR and ODx RS in breast cancer women in Taiwan. There was high concordance between the RI-DR and RS. The RI-DR is not inferior to the RS in predicting RFS in EBC patients. This study will fill the gap between the current and best practice in Chinese patients.

Determinants of Breast-Conserving Therapy in Early-Stage Breast Cancer Patients: A Nationwide Study.

INTRODUCTION: Evidence from previous studies and treatment guidelines suggested that breast-conserving therapy (BCT) is the treatment of choice for early-stage breast cancer. However, in the last decades, surgeons have noticed a high percentage of mastectomies done in this population. The aim of this study is to explore the factors associated with not choosing BCT among eligible patients with early-stage breast cancer. MATERIALS AND METHODS: This study uses a retrospective cohort design. Demographic and clinical characteristics derived from The Taiwan Cancer Registry Database, the National Health Insurance Database and the Death File Database from January 1, 2004 to December 31, 2014. Patients were followed until December 31, 2015. To explore the associated factors related to BCT, we used univariate and multivariate logistic regression analysis. RESULTS: A total sample of 25,967 stage I breast cancer patients was included. Among them, 12,191 underwent BCT and 13,776 underwent mastectomy as their primary treatment. The logistic regression analysis reveals that age, pay-for-performance (P4P) program participation, number of affected lymph nodes, tumor size and location, were determinants of BCT. Interestingly enough, histological type did not reach the significance level. CONCLUSION: This study shows that personal and clinical characteristics influence the treatment choice in stage 1 breast cancer patients.

Risk factors associated with conversion from nonmalignant to malignant diagnosis after surgical excision of breast papillary lesions.

PURPOSE: Management of papillary lesions of the breast identified during preoperative tissue diagnosis remains controversial. This study was designed to analyze the clinical factors associated with under-diagnosis of malignancy in breast papillary lesions. METHODS: Patients with a preoperative tissue diagnosis of benign or atypical papillary lesions, who received surgical excision between 1991 and 2005, were identified. Age of diagnosis, family history of breast cancer, presentation of nipple discharge, palpable mass, mammogram grading, size of lesion, and final pathological diagnosis were analyzed. Tissue sections were reviewed to confirm the diagnosis of malignancy and reasons of discrepancy. RESULTS: A total of 205 women with 228 papillary lesions were studied. The median age was 42 (range, 12-83) years. Malignancies were diagnosed after surgery in 21 cases (9.2%). Patients aged 45 years or older and atypical lesions according to fine needle aspiration cytology (FNAC) or core needle biopsy (CNB) were associated with higher risk for postoperative malignant diagnosis with P values of 0.0008 and < 0.0001, respectively. Pathology review of 19 lesions with malignancy revealed that reasons for preoperative nonmalignant diagnosis were borderline lesions in nine (47.3%), sampling problem in six (31.5%), interpretation error in three (15.7%) and uninterpretable sample in one (5.2%). CONCLUSIONS: In this cohort, 9.21% of preoperative nonmalignant papillary lesions were converted to malignant diagnosis after surgery. Atypical lesions and patients aged 45 years or older were significant factors associated with such conversion. Surgical excision should be considered for papillary lesions of breast, especially for patients with the identified risk factors.

Validation of the 18-gene classifier as a prognostic biomarker of distant metastasis in breast cancer.

We validated an 18-gene classifier (GC) initially developed to predict local/regional recurrence after mastectomy in estimating distant metastasis risk. The 18-gene scoring algorithm defines scores as: <21, low risk; ≥21, high risk. Six hundred eighty-three patients with primary operable breast cancer and fresh frozen tumor tissues available were included. The primary outcome was the 5-year probability of freedom from distant metastasis (DMFP). Two external datasets were used to test the predictive accuracy of 18-GC. The 5-year rates of DMFP for patients classified as low-risk (n = 146, 21.7%) and high-risk (n = 537, 78.6%) were 96.2% (95% CI, 91.1%-98.8%) and 80.9% (74.6%-81.9%), respectively (median follow-up interval, 71.8 months). The 5-year rates of DMFP of the low-risk group in stage I (n = 62, 35.6%), stage II (n = 66, 20.1%), and stage III (n = 18, 10.3%) were 100%, 94.2% (78.5%-98.5%), and 90.9% (50.8%-98.7%), respectively. Multivariate analysis revealed that 18-GC is an independent prognostic factor of distant metastasis (adjusted hazard ratio, 5.1; 95% CI, 1.8-14.1; p = 0.0017) for scores of ≥21. External validation showed that the 5-year rate of DMFP in the low- and high-risk patients was 94.1% (82.9%-100%) and 80.3% (70.7%-89.9%, p = 0.06) in a Singapore dataset, and 89.5% (81.9%-94.1%) and 73.6% (67.2%-79.0%, p = 0.0039) in the GEO-GSE20685 dataset, respectively. In conclusion, 18-GC is a viable prognostic biomarker for breast cancer to estimate distant metastasis risk.

Paravertebral Block Plus Thoracic Wall Block versus Paravertebral Block Alone for Analgesia of Modified Radical Mastectomy: A Retrospective Cohort Study.

BACKGROUND AND OBJECTIVES: Paravertebral block placement was the main anesthetic technique for modified radical mastectomy in our hospital until February 2014, when its combination with blocks targeting the pectoral musculature was initiated. We compared the analgesic effects of paravertebral blocks with or without blocks targeting the pectoral musculature for modified radical mastectomy. METHODS: We retrospectively collected data from a single surgeon and anesthesiologist from June 1, 2012, to May 31, 2015. Intraoperative sedatives and analgesic requirements, time to the first analgesic request, postoperative analgesic doses, patient satisfaction, and complications were compared. RESULTS: Fifty-four patients received a paravertebral block alone (PECS 0), and 46 received a paravertebral block combined with blocks targeting the pectoral musculature (PECS 1). The highest intraoperative effect-site concentration of propofol was significantly lower in the PECS 1 group than in the PECS 0 group [2.3 (1.5, 2.8) vs 2.5 (1.5, 4) µg/mL, p = 0.0014]. The intraoperative rescue analgesic dose was significantly lower in the PECS 1 group [0 (0, 25) vs 0 (0, 75) mg of ketamine, p = 0.0384]. Furthermore, the PECS 1 group had a significantly longer time to the first analgesic request [636.5 (15, 720) vs 182.5 (14, 720) min, p = 0.0001]. After further adjustment for age, body mass index, American Society of Anesthesiologists Physical Status classification, chronic pain history, incidence of a superficial cervical plexus block placement, and operation duration, blocks targeting the pectoral musculature were determined to be the only significant factor (hazard ratio, 0.36; 95% confidence interval, 0.23-0.58; p < 0.0001). Very few patients used potent analgesics including morphine and ketorolac; the cumulative use of morphine or ketorolac was similar in the study groups. However, the incidence of all analgesic use, namely morphine, ketorolac, acetaminophen, and celecoxib, was significantly lower in the PECS 1 group [3.5 (0, 6) vs 5 (0, 12), p < 0.0001]. CONCLUSIONS: Compared with the placement of a paravertebral block alone, combining blocks targeting the pectoral musculature with a paravertebral block for modified radical mastectomy reduced the sedative and analgesic requirements during operation and provided more effective postoperative analgesia.

An Eighteen-Gene Classifier Predicts Locoregional Recurrence in Post-Mastectomy Breast Cancer Patients.

We previously identified 34 genes of interest (GOI) in 2006 to aid the oncologists to determine whether post-mastectomy radiotherapy (PMRT) is indicated for certain patients with breast cancer. At this time, an independent cohort of 135 patients having DNA microarray study available from the primary tumor tissue samples was chosen. Inclusion criteria were 1) mastectomy as the first treatment, 2) pathology stages I-III, 3) any locoregional recurrence (LRR) and 4) no PMRT. After inter-platform data integration of Affymetrix U95 and U133 Plus 2.0 arrays and quantile normalization, in this paper we used 18 of 34 GOI to divide the mastectomy patients into high and low risk groups. The 5-year rate of freedom from LRR in the high-risk group was 30%. In contrast, in the low-risk group it was 99% (p < 0.0001). Multivariate analysis revealed that the 18-gene classifier independently predicts rates of LRR regardless of nodal status or cancer subtype.

Sonographic elastography improves the sensitivity and specificity of axilla sampling in breast cancer: a prospective study.

We describe a study to determine whether elastography of axillary lymph nodes (LNs) combined with B-mode ultrasound (US) is capable of differentiating the benign from the metastatic state in patients with breast cancer. B-mode US, elastography and fine-needle aspiration of 90 axillary lymph nodes from 89 female patients with breast cancer are described in this report. Five elastographic patterns were observed as defined by the percentages of high elasticity according to pattern of distribution and degree of hardness of the target LNs. B-mode US and elastography scores were combined to give the final scores. Sensitivity and specificity were 80% and 88%, respectively, for B-mode US alone, 86% and 90% for elastography alone and 84% and 98% for the combined assessment to differentiate the benign from the malignant state. The combination of B-mode US and elastography is capable of identifying metastatic axillary LNs from benign enlargement in patients with breast cancer.

Locoregional therapy in luminal-like and HER2-enriched patients with de novo stage IV breast cancer.

BACKGROUND: Locoregional therapy is rarely the standard of care for De Novo stage IV breast cancer but usually used for palliation of symptoms. This retrospective study aimed to determine whether surgery or radiation would contribute to survival benefit for this group of patients by examining the survival outcome through the disease molecular subtypes. MATERIALS AND METHODS: We reviewed 246 patients with de novo stage IV (M1) breast cancer treated at our hospital between 1990 and 2009. Multivariable Cox Analysis was used to evaluate the survival association with subtypes and clinicopathologic factors. RESULTS: Patients with luminal-like subtype are mostly premonopausal (66.9%, P = 0.0002), with abnormal CA 15-3 level at initial diagnosis (58.7%, P = 0.01), a higher rate of bony metastases (78.5%, P = 0.02), and a lower rate of liver metastases (22.3%, P < 0.0001). Patients with HER2-enriched and triple negative showed higher rate of nuclear grade III, up to 35% and 40%, respectively (P = 0.01). There is no difference in treatment options patient received: systemic chemotherapy up to 82.2 ~ 95% (p = 0.0705), locoregional treatment up to 40.0 ~ 51.2% (P-0.2571). The median overall survival was 23.1 months: luminal-like subtype 39.6 months, HER2-enriched subtype 17.9 months, and triple negative subtype 13.3 months, respectively (P < 0.0001). In multivariate analysis, poor prognostic factors included HER2-enriched (HR 2.2, P < 0.0001) and triple negative subtype (HR 4.3, P < 0.0001), liver metastasis (HR 1.9, P < 0.0001), lung metastasis (HR 1.4, P = 0.0153), and bone metastasis (HR 1.8, P = 0.0007). Subgroup analysis revealed that local treatments (surgery or radiotherapy) to primary/regional tumors achieved better survival in patients with luminal-like (3-year survival 66.4% vs. 34.4%, p = 0.0001) and HER2-enriched (3-year survival 41.6% vs. 8.8%, p = 0.0012) subtypes, but not in triple negative subtype (P = 0.9575). CONCLUSIONS: For better survival outcome, De Novo Stage IV breast cancer patients with luminal-like or HER2-enriched subtype should be offered local treatments when surgery and/or radiotherapy presents an option for proper control of the primary and regional tumors.

Validating a prognostic scoring system for postmastectomy locoregional recurrence in breast cancer.

PURPOSE: This study is designed to validate a previously developed locoregional recurrence risk (LRR) scoring system and further define which groups of patients with breast cancer would benefit from postmastectomy radiation therapy (PMRT). METHODS AND MATERIALS: An LRR risk scoring system was developed previously at our institution using breast cancer patients initially treated with modified radical mastectomy between 1990 and 2001. The LRR score comprised 4 factors: patient age, lymphovascular invasion, estrogen receptor negativity, and number of involved lymph nodes. We sought to validate the original study by examining a new dataset of 1545 patients treated between 2002 and 2007. RESULTS: The 1545 patients were scored according to the previously developed criteria: 920 (59.6%) were low risk (score 0-1), 493 (31.9%) intermediate risk (score 2-3), and 132 (8.5%) were high risk (score ≥4). The 5-year locoregional control rates with and without PMRT in low-risk, intermediate-risk, and high-risk groups were 98% versus 97% (P=.41), 97% versus 91% (P=.0005), and 89% versus 50% (P=.0002) respectively. CONCLUSIONS: This analysis of an additional 1545 patients treated between 2002 and 2007 validates our previously reported LRR scoring system and suggests appropriate patients for whom PMRT will be beneficial. Independent validation of this scoring system by other institutions is recommended.

The effect on improvement of recovery and pain scores of paravertebral block immediately before breast surgery.

OBJECTIVES: Paravertebral block (PVB) has the potential to reduce postoperative pain after breast surgery. The aim of the study was to investigate whether PVB performed immediately before surgery could affect the postoperative morbidities in terms of pain and emesis, and improve the quality of recovery (QoR) in patients after surgery for breast cancer. METHODS: Postoperative data were collected prospectively from two groups of patients undergoing unilateral breast surgery during the study period of 1 month. Forty consecutive patients received either solely general anesthesia (GA group, n=25) or GA plus ultrasound-guided PVB (GA+PVB group, n=15) for the surgery. Pain scores and areal distribution of pain were compared between the two groups 1 hour and 6 hours postoperatively and on the midmorning of postoperative Day 1 (POD1). The QoR scores were compared between the two groups 6 hours postoperatively and on the midmorning of POD1. Incidence of postoperative nausea and vomiting and doses of analgesics and narcotics given were also compared. RESULTS: Pain scores at rest were significantly lower in the GA+PVB group at all designated time points [1 hour (p<0.0001), 6 hours (p<0.0001), and on midmorning of POD1 (p=0.041)]. Pain scores with movements was also significantly lower at all time points in the GA+PVB group (1 hour, p<0.0001; 6 hours, p<0.0001; midmorning of POD1, p=0.0012). Areal distribution of pain at rest and with movement was wider in the GA group 1 hour and 6 hours postoperately but was identical to that of GA+ PVB group on the mid-morning of POD1 [1 hour postoperatively at rest (p<0.0001), with movement (p<0.0001); 6 hours postoperatively at rest (p=0.0018), with movement (p=0.0048)]. The QoR scores were significantly higher in the GA+PVB group at 6 hours (p<0.0001) and on midmorning of POD1 (p=0.0079). The incidences of postoperative nausea and vomiting were significantly lower in the GA+PVB group (p=0.0004). Doses of postoperative analgesics and narcotics were significantly less in the GA+PVB group (p<0.0001 and p=0.001, respectively). Time to first request for analgesics was significantly longer in the GA+PVB group (p=0.0002). CONCLUSIONS: PVB given before surgery in combination with GA could provide better postoperative analgesia and better QoR than did GA alone in patients undergoing surgery for unilateral breast cancer.

Radiotherapy can decrease locoregional recurrence and increase survival in mastectomy patients with T1 to T2 breast cancer and one to three positive nodes with negative estrogen receptor and positive lymphovascular invasion status.

PURPOSE: To define a subgroup of patients at high risk of locoregional recurrence (LRR) who might be benefit from postmastectomy radiotherapy in invasive breast cancer and tumor size <5 cm with one to three involved axillary lymph nodes (T1-2 N1). METHODS AND MATERIALS: Between April 1991 and December 2005, 544 patients with T1-2 N1 invasive breast cancer were treated with modified radical mastectomy. Of the 544 patients, 383 patients (70.4%) had no radiotherapy, and 161 patients (29.6%) received radiotherapy. We retrospectively compared these two patient groups. RESULTS: With a median follow-up of 40.3 months, LRR occurred in 40 (7.4%) of 544 patients. On univariate analysis, high nuclear grade (p = 0.04), negative estrogen receptor (ER) status (p = 0.001), presence of lymphovascular invasion (LVI) (p = 0.003), and no radiotherapy (p = 0.0015) were associated with a significantly higher rate of LRR. Negative ER status (hazard ratio = 5.1) and presence of LVI (hazard ratio = 2.5) were the risk factors for LRR with statistical significance in the multivariate analysis. Radiotherapy reduced the LRR in patients with the following characteristics: age <40 years, T2 stage, high nuclear grade, negative ER status, and presence of LVI. For 41 patients with negative ER and positive LVI status, radiotherapy can reduce LRR from 10 of 25 (40%) to 2 of 16 (12.5%) and increase the 5-year overall survival from 43.7% to 87.1%. CONCLUSION: Radiotherapy can reduce LRR and increase survival in T1-2 N1 breast cancer patients with negative ER status and presence of LVI.