Prognostic factors after isolated ipsilateral local and regional recurrence in HER2-negative luminal breast cancer: a multi-center retrospective study.

BACKGROUND: Although the incidence of isolated ipsilateral local and regional recurrence (IILRR) in human epidermal growth factor 2 (HER2)-negative luminal breast cancer is low, it is important because of its potential risk of distant metastasis and breast cancer related mortality. The aim of this study was to investigate prognostic factor and survival of IILRR using a large multi-center cohort. METHODS: Data on patients with HER2-negative luminal breast cancer between 2005 and 2015 were retrieved. The endpoint was IILRR rate, post-recurrence progression-free survival (P-PFS), and post-recurrence overall survival (P-OS). Prognostic factors for progression and overall survival (OS) after IILRR were assessed by multivariate analysis. RESULTS: Eighty (2.37%) patients experienced IILRR. Of them, 27 (33.7%) experienced a disease progression, including 23 (85.2%) who had distant metastasis. The median DFS was 48.5 months (range, 4-138 months). In 72.5% of cases, the first IILRR occurred after 3 years. Estimated 5-year P-PFS rates were 86.2%, 69.7%, 69.0%, 42.7%, and 82.2% for patients with age < 40 at diagnosis (p = 0.015), T1 stage (p = 0.012), stage I (p < 0.001), lymphovascular invasion (p = 0.003), and patients with post-recurrence endocrine therapy (p < 0.001), respectively. The 5-year Kaplan-Meier P-OS rate for patients was 81.4%. Post-recurrence endocrine therapy was independent factor for progression (HR: 0.176, p < 0.001) and OS (HR: 0.080, p < 0.001). CONCLUSIONS: Although there is no standardized treatment for IILRR yet, endocrine therapy after local resection plays a more important role in improving prognosis than chemotherapy or radiotherapy in HER2-negative luminal breast cancer.

Identifying long-term survivors among metastatic breast cancer patients undergoing primary tumor surgery.

PURPOSE: The prognostic role of primary tumor surgery in women with metastatic breast cancer at diagnosis is contentious. A subset of patients who will benefit from aggressive local treatment is needed to be identified. Using a nationwide database, we developed and validated a predictive model to identify long-term survivors among patients who had undergone primary tumor surgery. METHODS: A total of 150,043 patients were enrolled in the Korean Breast Cancer Registry between January 1990 and December 2014. Of these, 2332 (1.6%) presented with distant metastasis at diagnosis. Using Cox proportional hazards regression, we developed and validated a model that predicts survival in patients who undergo primary tumor surgery, based on the clinicopathological features of the primary tumor. RESULTS: A total of 2232 metastatic breast cancer patients were reviewed. Of these, 1541 (69.0%) patients had undergone primary tumor surgery. The 3-year survival rate was 62.6% in this subgroup. Among these patients, advanced T-stage, high-grade tumor, lymphovascular invasion, negative estrogen receptor status, high Ki-67 expression, and abnormal CA 15-3 and alkaline phosphatase levels were associated with poor survival. A prediction model was developed based on these factors, which successfully identified patients with remarkable survival (score 0-3, 3-year survival rate 87.3%). The clinical significance of the model was also validated with an independent dataset. CONCLUSIONS: We have developed a predictive model to identify long-term survivors among women who undergo primary tumor surgery. This model will provide guidance to patients and physicians when considering surgery as a treatment modality for metastatic breast cancer.

A one-day surgical-skill training course for medical students' improved surgical skills and increased interest in surgery as a career.

BACKGROUND: Despite many high-quality programs in basic surgical-skill education, the surgical skill of junior doctors varies widely. This, together with the waning interest in surgery as a career among medical students, is a serious issue confronted by hospitals and healthcare systems worldwide. We, therefore, developed and implemented an intensive one-day surgical-skill training course for two purposes; it would improve surgical skills and increase interest in surgery among medical students. METHODS: The surgical-skill training program is named Surgical Skill Weekend (SSW) and it includes hands-on training sessions for surgical-suturing techniques and advanced surgical procedures (i.e. laparoscopic and robot-assisted surgery), hybrid simulation sessions, and an operating-room session where aforementioned sessions are all put together. By the end of the program, students' improvements in surgical-suturing skills were assessed by experts in a form of checklist, and changes in the interest in a surgical career, if there were any, were answered by the students who participated in the program. RESULTS: A total of ninety-one (91) medical students participated in the 2015 and 2016 SSW courses. Their overall satisfaction level with the course was very high (Very satisfied: 78%, Quite satisfied: 22%). All of the participant's surgical-suturing skills significantly improved (median score range: 14-20, P < 0.05) and their interest in a surgical career increased significantly (from 56% to 81%, P < 0.05) by completing the program. CONCLUSIONS: An intensive and comprehensive surgical-skill training program for medical students can not only improve surgical-suturing skills but also increase interest in surgery as a career.

Sparganosis of the Unilateral Breast: A Case Report.

Sparganosis is a parasitic infection caused by the sparganum, the plercercoid of the genus Spirometra. The preoperative diagnosis of breast sparganosis is difficult in most cases because it is a rare parasitic infection less than 2% of all cases. We report a 62-year-old woman case of breast sparganosis that were confirmed by surgical removal of worms from the right breast. The radiologic images of the patient also revealed characteristic features of breast sparganosis. The patient described the migrating palpable breast mass, which strongly suggested the possibility of breast sparganosis. The treatment of choice and confirmative diagnosis for sparganosis are complete surgical extraction of the sparganum irrespective of infected site. Inspection of the mass site with detailed medical history and radiological examinations are important for preoperative diagnosis of sparganosis patients.

The distance between breast cancer and the skin is associated with axillary nodal metastasis.

BACKGROUND AND OBJECTIVES: More superficially located tumors may be more likely than deeper tumors to metastasize to the axillary nodes via the lymphatics. The aim of this study was to determine whether breast cancer distance from the skin affects axillary node metastasis, ipsilateral breast cancer recurrence, or recurrence-free survival. MATERIALS AND METHODS: A total of 1,005 consecutive patients with breast cancer who underwent surgery between January 2003 and December 2009 were selected. The distance of the tumor from the skin was measured from the skin to the most anterior hypoechoic leading edge of the lesion. RESULTS: In total, 603 (68%) patients had no axillary nodal metastasis, and 288 (32%) had axillary nodal metastasis. A breast cancer distance from the skin <3 mm induced more axillary nodal metastasis (P = 0.039). However, no significant correlation was observed between breast cancer distance from the skin <3 mm and ipsilateral breast cancer recurrence (P = 0.788) or recurrence-free survival (P = 0.353). CONCLUSIONS: Breast cancers located closer to the skin had a higher incidence of axillary nodal metastasis. Therefore, tumor distance from the skin should be considered when evaluating a patient with breast cancer and considering the risk of nodal metastasis.

Does papillary thyroid carcinoma have a better prognosis with or without Hashimoto thyroiditis?

BACKGROUND: It has been reported that the BRAF (V600E) mutation is related to a low frequency of background Hashimoto thyroiditis (HT); however, there are not many factors known to be related to the development of HT. The aim of this study was to determine whether patients with both papillary thyroid carcinoma (PTC) and HT show aggressive features, by investigating the clinicopathological features of HT in patients with PTC. METHODS: A database of patients with PTC who underwent thyroidectomy between October 2008 and August 2012 was collected and reviewed. All 2464 patients were offered a thyroidectomy, and DNA was extracted from the atypical cells in the surgical specimens for detection of the BRAF (V600E) mutation. Clinical and pathological characteristics were also investigated. RESULTS: Four hundred and fifty-two of 1945 (23.2%) patients were diagnosed with HT, and of these, 119 (72.1%) had a BRAF (V600E) mutation. HT was not significantly associated with the BRAF (V600E) mutation (P < 0.001) and extrathyroidal extensions (P = 0.005) but was associated with a low stage (P = 0.011) and female predominance (P < 0.001). In a subgroup analysis for gender, HT was associated with a low probability of BRAF (V600E) mutations in both genders (P < 0.001 for both females and males). Also, recurrence was significantly associated with HT (OR 0.297, CI 0.099-0.890, P = 0.030), lymph node ratio (OR 2.545, CI 1.092-5.931, P = 0.030), and BRAF (V600E) mutation (OR 2.075, CI 1.021-4.217, P = 0.044). However, there was no relationship with clinicopathological factors or with death. CONCLUSIONS: Our results show that HT in patients with PTC is associated with a low probability of BRAF (V600E) mutations. Moreover, HT was correlated with some factors that were associated with less aggressive clinical features and inversely related to recurrence. Therefore, these results may be useful to predict whether PTC concurrent with HT exhibits a better prognosis than PTC alone.

Prognostic influences of B-cell lymphoma 2-positive expression on late recurrence in breast cancer.

Purpose: B-cell lymphoma 2 (BCL2) has an antiapoptotic role, however, has resulted in it being a powerful favorable prognostic factor in breast cancer. Several studies revealed BCL2 is strongly associated with a lower rate of early recurrence after initial treatment in breast cancer patients, but study of a prolonged effect after 5 years is lacking. We investigated BCL2 as a prognostic factor in breast cancer in comparison to early and late recurrence. Methods: We retrieved data from 2,198 patients with primary breast cancer who underwent surgical treatment and adjuvant treatment at the breast cancer center between 2005 and 2015. Each molecular subtype was classified, and Ki-67 and BCL2 were also assessed by immunohistochemistry. BCL2 and the association between molecular subtypes were assessed in early and late recurrences, respectively. Five-year postrecurrence survival and BCL2 were also assessed. Results: The BCL2-positive group was associated with favorable clinicopathologic characteristics. The time to recurrence was significantly longer in the BCL2-positive group (P = 0.035). Late recurrence after 5 years was higher in the BCL2-positive group (P = 0.029). In multivariate survival analysis, tumor size and BCL2-positive expression were the only independent prognostic factors for late recurrence (P = 0.004). In the patients with recurrence, 5-year postrecurrence survival was significantly higher in the BCL2-positive group (P < 0.001). Conclusion: Our result showed that prognosis was better in BCL2-positive patients compared to BCL2-negative patients at late recurrence. We suggested that BCL2 expression could be used as a marker to help determine additional adjuvant therapy or extended hormone therapy in hormone-dependent breast cancer.

Present condition analysis of physician assistant in Korea.

This study intended to identify the need for the legalization and development of a systematic program for physician assistants (PAs) by understanding the actual state of PA operation in hospitals. In 114 hospitals assigned as resident training hospitals for surgery, a survey was conducted on the personnel working as PAs in those hospitals; the survey included general personal information, working conditions, training time, and satisfaction. A total of 192 PAs in surgery at 35 hospitals responded to the survey. The types of PAs are Surgical Assistant, Clinical Physician Assistant, Wound Ostomy Care Nurse, Coordinator, and Clinical Research Coordinator. Types of work PAs preformed are surgical assistance, wound dressing, educating patients, overlooking consultation, doing paper works, writing operation records, and confirming examination results which were ordered. The satisfaction level for the position which PAs hold were 29.1% and and satisfaction level which doctors see towards PA was 15%. The role and the job descriptions of PAs are not clear cut, there are many discrepancies among hospitals we studied. As a result, legalization and the implementation of standardized role of PAs will lead to increase level of satisfactions in the work force and the quality of work which PAs perform will be greater.

The different prognostic impact of age according to individual molecular subtypes in breast cancer.

Purpose: Young age at diagnosis has been considered a poor prognostic factor. However, considering young age itself as an independent poor prognostic factor for all breast cancers is unwarranted. We analyzed the different prognostic effects of age as a prognostic factor according to molecular subtype. Methods: We retrieved data from 1,819 patients with primary breast cancer at the breast cancer center between 2007 and 2012. We classified each molecular subtype in 3 age cohorts (<40, 40-50, and >50 years). The associations of age and molecular subtypes with relapse-free survival (RFS) and disease-specific survival (DSS) were assessed. Results: Patients aged <40 years showed a poor histologic grade, hormone receptor negative expression than older patients, and had a higher proportion of triple-negative breast cancer (TNBC) (P < 0.001). This was thought to have led to a significantly shorter RFS than that of older patients (P < 0.001). In the subgroup analysis according to molecular subtypes, the poorer RFS was observed only in patients aged <40 years with luminal type breast cancer (P < 0.001). Age was an independent prognostic factor of RFS in luminal-type breast cancer (P = 0.001). However, no difference in RFS between age groups was found for patients with other subtypes (human epidermal growth factor receptor 2 overexpression, TNBC). No significant effect between age groups was found in DSS for patients with all molecular subtypes. Conclusion: Age at diagnosis of breast cancer affected prognosis differently according to molecular subtype. Age itself is not an independent prognostic factor. Age of <40 years showed a limited worse prognostic impact of recurrence in luminal type breast cancer only.

Metastatic breast cancer from a hepatocellular carcinoma: a case report.

Breast metastases from extramammary malignancies are rare. Here, we report a case of breast metastasis from hepatocellular carcinoma (HCC) after breast mass excision in a 63-year-old woman. A new breast nodule was noticed after transarterial chemoembolization, transarterial radioembolization, and stereotactic body radiation therapy for HCC. Breast ultrasound and core needle biopsy were performed to differentiate between the breast tumors. The biopsy result was invasive breast carcinoma, and wide excision of the breast was performed. The final pathological diagnosis was HCC breast metastasis based on histological findings and immunohistochemical staining results. After 9 months of follow-up, HCC and breast metastasis recurred. Despite palliative treatment, the patient died due to complications and general health deterioration. Although breast metastasis due to HCC is very rare, HCC breast metastasis should be considered when a new breast mass is discovered in a patient with a history of HCC for effective treatment and management.

A N0 Predicting Model for Sentinel Lymph Node Biopsy Omission in Early Breast Cancer Upstaged From Ductal Carcinoma in Situ.

BACKGROUND: A prediction model with high sensitivity for the detection of negative axillary involvement can reduce additional axillary surgery in patients with ductal carcinoma in situ (DCIS) upstaged to invasive cancer while saving patients with pure DCIS from unnecessary axillary surgeries. Using a nationwide database, we developed and validated a scoring system for guidance in selective sentinel lymph node biopsy omission. PATIENTS AND METHODS: A total of 41,895 patients with clinically node-negative breast cancer from the Korean Breast Cancer Registry were included. The study cohort was randomly divided for the development and validation of the prediction model. Missing data were filled in using multiple imputation. Factors that were significantly associated with axillary lymph node (ALN) metastasis in > 50% of datasets were included in the final prediction model. RESULTS: The frequency of ALN metastasis in the total cohort was 24.5%. After multivariable logistic regression analysis, variables that were associated with ALN metastasis were palpability, multifocality, location, size, histologic type, grade, lymphovascular invasion, hormone receptor expression, and Ki-67 level. A scoring system was developed using these factors. The areas under the receiver operating characteristic curve for the scoring system was 0.750 in both training and validating sets. The cutoff value for performing sentinel lymph node biopsy was determined as a score of 4 to obtain prediction sensitivity higher than 95%. CONCLUSIONS: A scoring system to predict the probability of ALN metastasis was developed and validated. The application of this system in the clinic may reduce unnecessary axillary surgeries in patients with DCIS and minimize additional axillary surgery for upstaged patients with invasive cancer.

Clinical Differences in Triple-Positive Operable Breast Cancer Subtypes in Korean Patients: An Analysis of Korean Breast Cancer Registry Data.

PURPOSE: Triple-positive breast cancer is defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) positivity. Several systemic breast cancer therapies target hormonal and HER2 responsiveness. We compared clinical outcomes of triple-positive disease with those of HER2-enriched and luminal HER2-negative disease and investigated the clinical efficacy of anti-HER2 therapy for triple-positive disease. METHODS: We retrospectively compared overall and recurrence-free survival among cases included in the Korean Breast Cancer Society (KBCS) and Seoul St. Mary's Hospital breast cancer registries and the therapeutic efficacy of trastuzumab for triple-positive and HER2-enriched cases. RESULTS: KBCS registry data (2006-2010; median follow-up, 76 months) indicated that patients with triple-positive breast cancer had intermediate survival between those with luminal A and HER2-enriched subtypes (p<0.001). Trastuzumab did not improve overall survival among patients with triple-positive breast cancer (p=0.899) in contrast to the HER2-enriched subtype (p=0.018). Seoul St. Mary's Hospital registry data indicated similar recurrence-free survival outcomes (p<0.001) and a lack of improvement with trastuzumab among patients with triple-positive breast cancer (median follow-up, 33 months; p=0.800). Multivariate analysis revealed that patients with triple-positive breast cancer had better overall survival than those with HER2-enriched disease and similar survival as those with the luminal A subtype (triple-positive: hazard ratio, 1.258, p=0.118; HER2-enriched: hazard ratio, 2.377, p<0.001). CONCLUSION: Our findings showed that anti-HER2 therapy was less beneficial for treatment of triple-positive breast cancer than for HER2-enriched subtypes of breast cancer, and the triple-positive subtype had a distinct prognosis.

Improved Model for Predicting Axillary Response to Neoadjuvant Chemotherapy in Patients with Clinically Node-Positive Breast Cancer.

PURPOSE: Pathological complete response (pCR) of axillary lymph node (LN) is frequently achieved in patients with clinically node-positive breast cancer after neoadjuvant chemotherapy (NAC). Treatment of the axilla after NAC is not well established and the value of sentinel LN biopsy following NAC remains unclear. This study investigated the predictive value of axillary response following NAC and evaluated the predictive value of a model based on axillary response. METHODS: Data prospectively collected on 201 patients with clinically node-positive breast cancer who were treated with NAC and underwent axillary LN dissection (ALND) were retrieved. A model predictive of axillary pCR was developed based on clinicopathologic variables. The overall predictive ability between models was compared by receiver operating characteristic (ROC) curve analysis. RESULTS: Of 201 patients who underwent ALND after NAC, 68 (33.8%) achieved axillary pCR. Multivariate analysis using axillary LN pCR after NAC as the dependent variable showed that higher histologic grade (p=0.031; odds ratio [OR], 2.537; 95% confidence interval [CI], 1.087-5.925) and tumor response rate ≥47.1% (p=0.001; OR, 3.212; 95% CI, 1.584-6.515) were significantly associated with an increased probability of achieving axillary pCR. The area under the ROC curve for estimating axillary pCR was significantly higher in the model that included tumor response rate than in the model that excluded this rate (0.732 vs. 0.649, p=0.022). CONCLUSION: Tumor response rate was the most significant independent predictor of axillary pCR in response to NAC. The model that included tumor response rate was a significantly better predictor of axillary pCR than the model that excluded tumor response rate.

BCL2 as a Subtype-Specific Prognostic Marker for Breast Cancer.

PURPOSE: B-cell lymphoma 2 (BCL2) is an antiapoptosis protein and an important clinical breast cancer prognostic marker. As the role of BCL2 is dependent on the estrogen receptor (ER) status, this effect might differ according to molecular subtypes. The aim of this study was to evaluate the relationship between the prognostic outcomes and BCL2 expression among the molecular subtypes. METHODS: We retrieved the data of 1,356 patients who were newly diagnosed with malignant breast cancer between November 2006 and November 2011. Immunohistochemistry was used to measure ER, progesterone receptor, human epidermal growth factor receptor 2 (HER2), Ki-67, and BCL2 expression. We classified breast cancer into five molecular subtypes based on the 13th St. Gallen International Expert Consensus, including luminal A, luminal B (HER2-negative), luminal B (HER2-positive), HER2-overexpression, and triple-negative subtypes. We analyzed the clinicopathological features and assessed the correlation between BCL2 expression and clinical outcomes, such as relapse-free survival (RFS) and disease-specific survival (DSS) according to the five molecular subtypes. RESULTS: A total of 605 cases of breast cancer (53.8%) showed BCL2 expression. BCL2-positive expression was associated with young age (<50 years, p=0.036), lower histological grade (p<0.001), low Ki-67 level (<14%, p<0.001), hormone receptor positivity (p<0.001), HER2 negativity (p<0.001), luminal breast cancer (p<0.001), and low recurrence rate (p=0.016). BCL2-positive expression was also associated with favorable 5-year RFS (p=0.008, 91.4%) and DSS (p=0.036, 95.6%) in all the patients. BCL2-positive expression in luminal A breast cancer resulted in significantly favorable 5-year RFS and DSS (p=0.023 and p=0.041, respectively). However, BCL2 expression was not associated with the prognosis in the other subtypes. CONCLUSION: The prognostic role of BCL2 expression in breast cancer is subtype-specific. BCL2 expression differs according to the molecular subtype and is a good prognostic marker for only luminal A breast cancer.

Is adjuvant chemotherapy omissible in women with T1-2 stage, node-positive, luminal A type breast cancer?

PURPOSE: The aim of this study was to evaluate whether hormonal breast cancer therapy without systemic chemotherapy is feasible in adjuvant settings in luminal A breast cancer. METHODS: A database of 879 patients who underwent breast cancer surgery enrolled between January 2003 and December 2011 was reviewed. Patients with luminal A cancers were selected and grouped into those who received adjuvant hormonal therapy with (group C+) or without (group C - ) adjuvant systemic therapy. RESULTS: In a multivariable analysis, axillary lymph node (ALN) metastasis was the only independent factor that revealed significantly different between the two groups in disease-free survival (DFS). The 5-year cumulative DFS was 82.3 versus 76.2% (P = 0.700) and overall survival (OS) was 83.9 versus 100% (P = 0.483) for C+ versus C - breast cancer, respectively. CONCLUSION: In our study, adjuvant chemotherapy in luminal A, T1-2N+ cancer showed no significant difference for DFS. We believe that the role of adjuvant chemotherapy for these women with hormonal therapy might have little benefit.