Gigantomastia is a rare condition characterized by excessive breast growth. It has been reported that the majority of gigantomastia cases occur during either pregnancy or puberty. We were presented with a rare case of gigantomastia associated with neither pregnancy nor puberty, and successfully treated it with reduction mammaplasty and free nipple graft. This idiopathic gigantomastia is the very first case in Korea, and adds to the worldwide total of 9 reported cases.
Gigantomastia; Breast; Reduction; Mammaplasty
Occult breast cancer is a type of breast cancer without any symptoms on the breasts or any abnormalities upon radiologic examination such as mammography. In males, there are few cases of breast cancer, the rate of diagnosis of occult breast cancer is very low, and little is known about this disease. We experienced two cases of occult breast cancers manifesting as axillary lymph node metastasis in men. They had a palpable lesion on axillary area several years ago and had not seen a doctor about it. As such there was no abnormality on evaluations for cancer except for axillary lymph node showing signs of carcinoma (primary or metastatic) on biopsy and estrogen receptor-positive and progesterone receptor-positive on immunohistochemistry. The patients were diagnosed with occult breast cancer, and treatments were performed. Herein, we report the rare cases of occult breast cancers in men.
Axilla; Breast neoplasms; Male; Neoplasm metastasis; Occult primary neoplasms
Internal mammary lymph node (IMLN) metastasis is an important prognostic indicator in breast cancer. However, the necessity of internal mammary sentinel lymph node biopsy for accurate staging, for choosing adjuvant treatment, and as a prognostic indicator, has remained controversial.
From January 2001 to December 2006, 525 female breast cancer patients underwent radical surgery after preoperative lymphatic scintigraphy. We retrospectively analyzed the follow-up results, recurrences, and deaths of all patients.
There was no significant difference in the clinicopathological characteristics between the axilla and the IMLN groups. The median follow-up period was 118.8 months (range, 7-122 months) in the axilla group and 107.7 months (range, 14-108 months) in the IMLN group. During the median follow-up period, the breast cancer-related death rate in the axilla group was 3.6%, which was not significantly different from that of the IMLN group (1.3%) (p=0.484). The five-year survival rates did not differ between the two groups (p=0.306). The overall recurrence rate and the locoregional recurrence rate also did not differ between the two groups (p=0.835 and p=0.582, respectively). The recurrence rate of IMLN (both ipsilateral and contralateral) metastasis was very low, accounting for 0.5% in the axilla group and 1.3% in the IMLN group (p=0.416).
The long-term follow-up results showed that there was no significant difference in both overall outcome and regional recurrence between the two groups. Therefore, the requirement for identification of nodal basins outside the axilla or IMLN sentinel biopsy should be reconsidered.
Breast; Carcinoma; Internal mammary; Prognosis; Sentinel lymph node biopsy
To determine the effects of new breast cancer treatments and to provide a baseline for monitoring the development of breast cancer in Korean women, we conducted an analysis at our institution to determine long-term clinicopathological features, survival rates, and prognostic factors.
Materials and Methods
This study retrospectively analyzed 2,403 patients between Sep 1994 and Dec 2002, who underwent breast cancer surgery at Samsung Medical Center in Korea. Demographic data, pathologic records and surgical records were collected.
After a median follow-up duration of 121.9 (range: 2-158.1) months, the 5-year disease free survival (DFS) was 82.8% and the 10-year DFS was 74.7%. The 5-year and 10-year overall survival (OS) rates were 89.4% and 82.9%, respectively. Using multivariate analyses, we determined that the nodal status (p < 0.001), angioinvasion (p < 0.001), positive PR (p < 0.001), and C-erb-B2 (p < 0.001) were independent prognostic factors for OS. The frequency of breast conserving surgery was 33.9% before Dec 1999, and increased up to 44.1% by year Dec 2002.
Most of the prognostic variables and clinical characteristics of the Korean breast cancer patients were similar to those reported for Western populations. However, the age distribution in Korean patients seemed to be different from that in patients from Western countries.
Breast cancer; survival; disease free survival; breast conserving surgery
The aim of this study is to evaluate the results for the insertion of totally implantable central venous access devices (TICVADs) by surgeons.
Total 397 patients, in whom TICVADs had been inserted for intravenous chemotherapy between September 2008 and June 2014, were pooled. This procedure was performed under local anesthesia in an operation room. The insertion site for the TICVAD was mainly in the right-side subclavian vein. In the case of breast cancer patients, the subclavian vein opposite the surgical site was used for insertion.
The 397 patients included 73 males and 324 females. Primary malignant tumors were mainly colorectal and breast cancer. The mean operation time was 54 minutes (18-276 minutes). Operation-related complications occurred in 33 cases (8.3%). Early complications developed in 15 cases with catheter malposition and puncture failure. Late complications, which developed after 24 hours, included inflammation in 6 cases, skin necrosis in 6 cases, hematoma in 3 cases, port malfunction in 1 case, port migration in 1 case, and intractable pain at the port site in 1 case.
Insertion of a TICVAD under local anesthesia by a surgeon is a relatively safe procedure. Meticulous undermining of the skin and carefully managing the TICVAD could minimize complications.
Vascular access devices; Central venous catheterization; Maintenance chemotherapy
The anticancer property and cytoprotective role of selenium in chemotherapy have been reported. However, the combination effects of selenium on chemotherapy for advanced breast cancer have not yet been clearly defined. The purpose of this study was to investigate the combined effects of selenium on chemotherapy using docetaxel on breast cancer cell lines.
Under adherent culture conditions, two breast cancer cell lines, MDA-MB-231 and MCF-7, were treated with docetaxel at 500pM and selenium at 100nM, 1µM, or 10µM. Changes in cell growth, cell cycle duration, and degree of apoptosis after 72 hours in each treated group were evaluated.
In the MDA-MB-231 cells, the combination therapy group (docetaxel at 500pM plus selenium at 10µM) showed a significantly decreased percentage of cell growth (15% vs. 28%; P = 0.004), a significantly increased percentage of late apoptosis (63% vs. 26%; P = 0.001), and an increased cell cycle arrest in the G2/M phase (P = 0.001) compared with the solitary docetaxel therapy group. Isobologram analysis demonstrated the synergistic effect of the combination therapy in the MDA-MB-231 cells. However, in the MCF-7 cells, no significant differences in the percentage of cell growth apoptosis, the percentage of apoptosis, and the pattern of cell cycle arrest were noted between the combination therapy groups and the solitary docetaxel therapy group.
Our in vitro study indicated that the combination of selenium with docetaxel inhibits cell proliferation through apoptosis and cell arrest in the G2/M phase in MDA-MB-231 breast cancer cells.
Breast neoplasms; Selenium; Docetaxel; Combination drug therapy
Differentiated thyroid cancer has a good prognosis and high incidence in young women. Since endoscopic techniques were first recorded in 1996, surgical indications of endoscopic thyroidectomy have broadened. Therefore, the aim of this study is to investigate the usefulness of endoscopic thyroidectomy in clinically lymph node negative (cN0) thyroid cancer patients, based on oncologic completeness and safety, considering cosmetic outcomes.
From July 2009 to June 2011, a total of 166 cases had undergone endoscopic thyroidectomy using the BABA (bilateral axillo-breast approach) method or conventional open thyroidectomy by one surgeon. Finally, excluding 72 patients, 94 patients with cN0 thyroid cancer were divided into two groups according to operative methods and analyzed to compare differences between the two methods retrospectively (endoscopic group, n = 49; conventional open group, n = 45).
We practiced comparative analysis for clinicopathologic characteristics, surgical outcomes including postoperative complications, and recurred cases during follow-up periods of each group. The results showed there was a tendency for patients, young, women rather than men, and having small size of thyroid cancer, to prefer endoscopic surgery to open surgery. Meanwhile, in postoperative complications, there were no statistically significant differences. During short follow-up periods, no recurrence or mortality case was observed.
Endoscopic thyroidectomy is a feasible and safe method for the treatment of clinically lymph node negative (cN0) thyroid cancer.
Endoscopic thyroidectomy; Lymph nodes; Thyroid neoplasms
Follicular variant of papillary thyroid carcinoma (FVPTC), particularly the encapsulated subtype, often causes a diagnostic dilemma. We reconfirmed the molecular profiles in a large number of FVPTCs and investigated the efficacy of the preoperative mutational analysis in indeterminate thyroid nodules. BRAF V600E/K601E and RAS mutational analysis was performed on 187 FVPTCs. Of these, 132 (70.6%) had a point mutation in one of the BRAF V600E (n = 57), BRAF K601E (n = 11), or RAS (n = 64) genes. All mutations were mutually exclusive. The most common RAS mutations were at NRAS codon 61. FNA aspirates from 564 indeterminate nodules were prospectively tested for BRAF and RAS mutation and the surgical outcome was correlated with the mutational status. Fifty-seven and 47 cases were positive for BRAF and RAS mutation, respectively. Twenty-seven RAS-positive patients underwent surgery and all except one patient had FVPTC. The PPV and accuracy of RAS mutational analysis for predicting FVPTC were 96% and 84%, respectively. BRAF or RAS mutations were present in more than two-thirds of FVPTCs and these were mutually exclusive. BRAF mutational analysis followed by N, H, and KRAS codon 61 mutational analysis in indeterminate thyroid nodules would streamline the management of patients with malignancies, mostly FVPTC.
The Gail model is one of the most widely used tools to assess the risk of breast cancer. However, it is known to overestimate breast cancer risk for Asian women. Here, we validate the Gail model and the Korean model using Korean data, and subsequently update and revalidate the Korean model using recent data.
We validated the modified Gail model (model 2), Asian American Gail model, and a previous Korean model using screening patient data collected between January 1999 and July 2004. The occurrence of breast cancer was confirmed by matching the resident registration number with data from the Korean Breast Cancer Registration Program. The expected-to-observed (E/O) ratio was used to validate the reliability of the program, and receiver operating characteristics curve analysis was used to evaluate the program's discriminatory power. There has been a rapid increase in the incidence of breast cancer in Korea, and we updated and revalidated the Korean model using incidence and mortality rate data from recent years.
Among 40,229 patients who were included in the validation, 161 patients were confirmed to have developed breast cancer within 5 years of screening. The E/O ratios and 95% confidence intervals (CI) were 2.46 (2.10-2.87) for the modified Gail model and 1.29 (1.11-1.51) for the Asian American Gail model. The E/O ratio and 95% CI for the Korean model was 0.50 (0.43-0.59). For the updated Korean model, the E/O ratio and 95% CI were 0.85 (0.73-1.00). In the discriminatory power, the area under curve and 95% CI of the modified Gail model, Asian American Gail model, Korean model and updated Korean model were 0.547 (0.500-0.594), 0.543 (0.495-0.590), 0.509 (0.463-0.556), and 0.558 (0.511-0.605), respectively.
The updated Korean model shows a better performance than the other three models. It is hoped that this study can provide the basis for a clinical risk assessment program and a future prospective study of breast cancer prevention.
Breast neoplasms; Risk assessment; Validation studies
The study was designed to investigate postoperative nausea and vomiting (PONV) in low- and high-dose remifentanil regimens for total intravenous anaesthesia (TIVA) in adult female patients with American Society of Anaesthesiologists physical status classification I undergoing local breast excision. Propofol and remifentanil 5 ng·mL−1 (L group) or 10 ng·mL−1 (H group) were administered for anaesthesia induction and maintenance. Propofol was titrated within range of 0.1 μg·mL−1 to maintain bispectral index (BIS) values between 40 and 60. Haemodynamic parameters during the intra- and postoperative periods and 24 h postoperative visual analogue scale (VAS) and PONV were evaluated. Each group with 63 patients was analyzed. The H group showed higher use of remifentanil and lower use of propofol, with similar recovery time. Mean systemic arterial blood pressure (MBP), heart rate, and BIS did not differ significantly before and after endotracheal intubation in the H group. However, significant increases in MBP and BIS were apparent in the L group. Postoperative VAS, PONV incidence and scale, and Rhodes index did not differ significantly between the two groups. In conclusion, TIVA with high-dose remifentanil did not aggravate PONV with similar postoperative pain, compared with low-dose remifentanil. Furthermore, high-dose remifentanil showed more haemodynamic stability after endotracheal intubation. This trial is registered with KCT0000185.
Thiopental and propofol have been widely used for general anesthesia induction, but their impacts on cardiac function have not been well described. A recent study speculated that anesthesia induction using propofol 2 mg/kg transiently reduced left ventricular (LV) contraction by analyzing tissue Doppler-derived imaging (TDI) during induction phase. The purpose of this study was to analyze and to compare the impacts of propofol- and thiopental-induction on LV function.
Twenty-four female patients with normal LV function undergoing non-cardiac surgery were randomly administered intravenous bolus thiopental (5 mg/kg, Thiopental-group, n = 12) or propofol (2 mg/kg, Propofol-group, n = 12) for anesthesia-induction. TDI of septal mitral annular velocity during systole (S'), early diastole (e') and atrial contraction (a') were determined by transthoracic echocardiography before and 1, 3, and 5 minutes after thiopental/propofol administration (T0, T1, T2, and T3, respectively).
The bispectral index and systolic blood pressure declined significantly during anesthesia induction in both groups, however, more depressed in Thiopental-group compared with those in Propofol-group at T2 and T3 (all, p < 0.05). Among TDI two parameters demonstrated a significant inter-group difference: the S' in propofol was lower than that in Thiopental-group at T3 (p = 0.002), and a' velocities were persistently lower in Propofol-group, compared with same time values in Thiopental-group (T1, T2, and T3: p = 0.025, 0.007, and 0.009, respectively).
Anesthesia induction using propofol revealed a more persistent and profound decline of LV and atrial contraction than that using thiopental. Further studies are needed to understand the clinical implication.
Intraoperative; Echocardiography; Doppler; Thiopental; Propofol
To present the author's experience with various treatment methods of granulomatous lobular mastitis (GLM) and to determine effective treatment methods of GLM.
Fifty patients who were diagnosed with GLM were classified into five groups based on the initial treatment methods they underwent, which included observation (n = 8), antibiotics (n = 3), steroid (n = 13), drainage (n = 14), and surgical excision (n = 12). The treatment processes in each group were examined and their clinical characteristics, treatment processes, and results were analyzed respectively.
Success rates with each initial treatment were observation, 87.5%; antibiotics, 33.3%; steroids, 30.8%; drainage, 28.6%; and surgical excision, 91.7%. In most cases of observation, the lesions were small and the symptoms were mild. A total of 23 patients underwent surgical excision during treatment. Surgical excision showed particularly fast recovery, high success rate (90.3%) and low recurrence rate (8.7%).
The clinical course of GLM is complex and the outcome of each treatment type are variable. Surgery may play an important role when a lesion is determined to be mass-forming or appears localized as an abscess pocket during breast examination or imaging study.
Breast; Granulomatous mastitis; Treatment; Excision
Breast cancer is one of the most frequent malignancies in Korean women, and its incidence is increasing at a rapid rate. Since 1996, the Korean Breast Cancer Society has collected nationwide breast cancer data using an online registration program and analyzed the data biennial. The purpose of this study was to evaluate the characteristics of Korean breast cancer and to analyze changes in these characteristics over the period of time.
Data were collected from 41 medical schools (74 hospitals), 24 general hospitals, and 6 private clinics. Data on the total number, gender, and age of newly-diagnosed breast cancer patients were collected through a questionnaire. Additional data were collected and analyzed from the online database.
In 2010, 16,398 patients in Korea were newly diagnosed with breast cancer. The crude incidence rate of female breast cancer was 67.2 cases per 100,000, and the median age at diagnosis was 49 years. The incidence of breast cancer was highest in patients aged between 40 and 49 years. Since 1996, there has been a significant increase in the proportion of early-stage cancers (detected in stage 1 or 2), the percentage of estrogen receptor-positive cancers, and in the proportion of patients receiving breast-conserving surgery.
The incidence and clinical characteristics of Korean breast cancer are slowly changing to the patterns of Western countries. To understand changing patterns in the characteristics of Korean breast cancer, the nationwide data should be continuously analyzed.
Breast neoplasms; Korea; Online registration program
Bone is the most common metastatic organ in patients with breast cancer. The most significant clinical symptom of bone metastasis is pain which reduces quality of life in cancer patients. We report a case of chest wall reconstruction after partial sternal resection for solitary sternal metastasis and modified radical mastectomy in a patient with locally advanced breast cancer. The sternal defect was reconstructed with a 2 mm thick Gore-Tex patch. Postoperative pain was acceptable and the patient was discharged without any complications. The patient received the endocrine and bisphosphonate therapy combined with chemotherapy and radiotherapy. No recurrence or complications were observed during a follow-up period of 36 months. We describe our good surgical management results of sternal metastatic lesion in a patient with locally advanced breast cancer. We suggest that simultaneous sternectomy is a safe and curative surgical method for a solitary sternal metastasis when no evidence of systemic spread is noted.
Breast carcinoma; Metastasectomy; Neoplasm metastasis; Sternum
Prevalence and phenotype of BRCA mutation can vary by race. The purpose of this study is to evaluate the prevalence of BRCA1/2 mutations in non-familial breast cancer patients with high risks in Korea. A subset of 758 patients was selected for this study from the KOHBRA nationwide multicenter prospective cohort study. Mutations in BRCA1/2 genes were tested using fluorescent-conformation sensitive gel electrophoresis, denaturing high performance liquid chromatography or direct sequencing. Mutation of BRCA1/2 genes were identified in 65 (8.6%) patients among total 758 patients [BRCA1 mutation: 25 (3.3%), BRCA2 mutation: 40 (5.3%)]. According to risk groups, mutation of BRCA1/2 genes were identified in 53 (8.5%) of 625 early onset patients (age ≤40), in 22 (17.7%) of 124 bilateral breast cancer patients, in 3 (50.0%) of 6 breast and ovarian cancer patients, in one (5.9%) of 17 male breast cancer patients, in 5 cases (7.6%) of 66 multiple organ cancer patients. The most common mutation was 509C>A for BRCA1 and 7708C>T for BRCA2. The prevalence of BRCA1/2 mutations by age in early onset patients was significantly different (age <35 vs age ≥35; 10.0 vs 2.9%, p = 0.0007). BRCA1/2 mutations for non-familial Korean breast cancer patients were detected at a high rate, particularly, in patients with early onset of less than 35 years of age, bilateral breast cancer, and breast and ovarian cancer. Individualized genetic counseling should be offered for non-familial breast cancer patients with these risk factors.
BRCA1; BRCA2; Hereditary breast cancer; Korean; Non-familial; Prevalence
Mucinous carcinoma (MC) of the breast is a rare histologic type of mammary neoplasm. The objective of this study was to evaluate the long-term disease-free survival (DFS) and overall survival (OS) of MC.
We conducted a retrospective analysis of all MC cases reported to a database between 1994 and 2010. Clinicopathological characteristics and survival of 268 MC cases were reviewed and compared with 2,455 invasive ductal carcinoma-not otherwise specified (IDC-NOS) cases.
The MC cases were of a younger age, involved less lymph nodes, lower stage, more expression of hormonal receptors, and less HER2 overexpression compared to the IDC-NOS cases. The 5-year DFS rate for MC was 95.2% compared to 92.0% for IDC-NOS. The 5-year OS rate for MC was 98.9% compared to 94.9% for IDC-NOS. Multivariate analysis using Cox regression revealed that the mucinous type was a significant prognostic factor for DFS with lower nodal status (N stage) and hormonal therapy. For OS, only N stage was the most significant prognostic factor followed by adjuvant chemotherapy and adjuvant hormonal therapy.
MC was shown to be associated with a better DFS than IDC-NOS, but it had a similar OS. Nodal status and adjuvant therapy appear to be more significant predictors of prognosis than histologic subtype.
Adenocarcinoma; Breast; Invasive ductal carcinoma; Mucinous; Prognosis
The frequency of immediate breast reconstruction (IBR) is increasing, and the types of reconstruction used are diverse. Adjuvant chemotherapy is a life-saving intervention in selected high-risk breast cancer patients. The aim of our study was to determine how IBR and type of reconstruction affect the timing of the initiation of chemotherapy.
We obtained data from female breast cancer patients treated by mastectomy with IBR (IBR group) and without IBR (mastectomy only group) who received adjuvant chemotherapy between January 1, 2008, and December 31, 2010. We retrospectively collected data including patient characteristics, disease characteristics, treatment details, and treatment outcomes from our institutional electronic patient database and medical treatment records. The reconstruction types were categorized as deep inferior epigastric perforator (DIEP) flap, latissimus dorsi (LD) flap and tissue expander/implant (TEI).
In total, 595 patients were included in this study. Of these patients, 43 underwent mastectomy with IBR (IBR group) and 552 patients did not undergo reconstruction (mastectomy only group). There was significant difference in the timing of the initiation of chemotherapy between the two groups (p<0.0001). There were no cases of delays of more than 12 weeks. In the IBR group, 20 patients received TEI, 9 patients were treated by the insertion DIEP flaps, and 14 patients were treated by LD flaps. There were no significant differences in the timing of chemotherapy according to the type of reconstruction (p=0.095).
IBR delays the initiation of chemotherapy, but does not lead to omission or significant clinical delay in chemotherapy. Further, the type of reconstruction does not affect the timing of chemotherapy.
Adjuvant chemotherapy; Breast neoplasms; Breast reconstruction
Recently, several clinicians have reported the advantages of simplicity and cosmetic satisfaction of absorbable mesh insertion. However, there is insufficient evidence regardint its long-term outcomes. We have investigated the surgical complications and postoperative examination from the oncologic viewpoint.
Materials and Methods
From February 2008 to March 2009, 34 breast cancer patients underwent curative surgery with absorbable mesh insertion in Samsung Medical Center. Patient characteristics and follow up results including complications, clinical and radiological findings were retrospectively investigated.
The mean age of the study population was 50.1±8.9 years old (range 31-82) with a mean tumor size of 3±1.8 cm (range 0.8-10.5), and the excised breast tissue showed a mean volume of 156.1±99.8 mL (range 27-550). Over the median follow-up period of 18±4.6 months (range 3-25), mesh associated complications, including severe pain or discomfort, edema, and recurrent fluid collection, occurred in nine patients (26.5%). In three cases (8.8%), recurrent mastitis resulted in mesh removal or surgical intervention. In the postoperative radiologic survey, the most common finding was fluid collection, which occurred in five patients (16.1%), including one case with organizing hematoma. Fat necrosis and microcalcifications were found in three patients (9.7%).
Absorbable mesh insertion has been established as a technically feasible, time-saving procedure after breast excision. However, the follow-up results showed some noticeable side effects and the oncologic safety of the procedure is unconfirmed. Therefore, we suggest that mesh insertion should be considered only in select cases and should be followed-up carefully.
Breast neoplasms; mastectomy; segmental; absorbable implants
The aim of the current study was to determine the incidence, clinical presentation, and treatment outcomes of "bone-only metastases" in patients with breast cancer and to analyze the impact of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status on prognosis.
Materials and Methods
Between 1994 and 2007, of 968 patients with metastatic breast cancer who underwent palliative management at Samsung Medical Center, 565 (57%) relapsed with distant metastases. Of the 968, 146 (15%) had bone-only metastases during a median follow-up period of 75 months. Among the 146 patients with bone-only metastases, 122 (84%) were relapsed patients after curative surgery and 24 (26%) were initially metastatic cases.
The median time from primary surgery to bone-only metastases of the 122 patients was 37 months (95% confidence interval [CI], 27 to 46 months). Bone-only metastases were more common in the HR-positive group than in the other subtypes (85% for HR+; 8.2% for HER2+; 6.8% for triple negative. Among all 146 patients, 75 (51%) were treated with hormone therapy. The median post-relapse progression-free survival was 15 months (95%CI, 13 to 17 months). The median overall survival was much longer in the HR+ patients than the HER2+ and triple negative breast cancer patients with marginal statistical significance (65 vs. 40 vs. 40 months, p=0.077).
Breast cancer patients with "bone-only metastases" had excellent clinical outcomes. Further study is now warranted to reveal the underlying biology that regulates the behavior of this indolent tumor, as it should identify 'favorable tumor characteristics' in addition to 'favorable preferential metastatic site.'
Bone; Neoplasm metastasis; Breast neoplasms; Estrogen receptors; Progesterone receptors; HER2
Epithelial-mesenchymal transition (EMT), a switch of polarized epithelial cells to a migratory, fibroblastoid phenotype, is considered a key process driving tumor cell invasiveness and metastasis. Using breast cancer cell lines as a model system, we sought to discover gene-expression signatures of EMT with clinical and mechanistic relevance. A supervised comparison of epithelial and mesenchymal breast cancer lines defined a 200-gene EMT signature that was prognostic across multiple breast cancer cohorts. Immunostaining of LYN, a top-ranked EMT signature gene and Src-family tyrosine kinase, was associated with significantly shorter overall survival (P=0.02), and correlated with the basal-like (“triple-negative”) phenotype. In mesenchymal breast cancer lines, RNAi-mediated knockdown of LYN inhibited cell migration and invasion, but not proliferation. Dasatinib, a dual-specificity tyrosine kinase inhibitor, also blocked invasion (but not proliferation) at nanomolar concentrations that inhibit LYN kinase activity, suggesting that LYN is a likely target and invasion a relevant endpoint for dasatinib therapy. Our findings define a prognostically-relevant EMT signature in breast cancer, and identify LYN as a mediator of invasion and possible new therapeutic target (and theranostic marker for dasatinib response), with particular relevance to clinically-aggressive basal-like breast cancer.
Breast cancer; epithelial-mesenchymal transition; transcriptional profiling; LYN; dasatinib
A 70-gene prognostic signature has prognostic value in patients with node-negative breast cancer in Europe. This diagnostic test known as "MammaPrint™ (70-gene prognostic signature)" was recently validated and implementation was feasible. Therefore, we assessed the 70-gene prognostic signature in Korean patients with breast cancer. We compared the risk predicted by the 70-gene prognostic signature with commonly used clinicopathological guidelines among Korean patients with breast cancer. We also analyzed the 70-gene prognostic signature and clinicopathological feature of the patients in comparison with a previous validation study.
Forty-eight eligible patients with breast cancer (clinical T1-2N0M0) were selected from four hospitals in Korea. Fresh tumor samples were analyzed with a customized microarray for the 70-gene prognostic signature. Concordance between the risk predicted by the 70-gene prognostic signature and risk predicted by commonly used clinicopathological guidelines (St. Gallen guidelines, National Institutes of Health [NIH] guideline, and Adjuvant! Online) was evaluated.
Prognosis signatures were assessed in 36 patients. No significant differences were observed in the clinicopathological features of patients compared with previous studies. The 70-gene prognosis signature identified five (13.9%) patients with a low-risk prognosis signature and 31 (86.1%) patients with a high-risk prognosis signature. Clinical risk was concordant with the prognosis signature for 29 patients (80.6%) according to the St. Gallen guidelines; 30 patients (83.4%) according to the NIH guidelines; and 23 patients (63.8%) according to the Adjuvant! Online. Our results were different from previous validation studies in Europe with about a 40% low-risk prognosis and about a 60% high-risk prognosis. The high incidence in the high-risk group was consistent with data in Japan.
The results of 70-gene prognostic signature of Korean patients with breast cancer were somewhat different from those identified in Europe. This difference should be studied as whether there is a gene disparity between Asians and Europeans. Further large-scale studies with a follow-up evaluation are required to assess whether the use of the 70-gene prognostic signature can predict the prognosis of Korean patients with breast cancer.
Breast neoplasms; Gene expression profiling; Korea
To study clinical features and patterns of recurrence after breast-conserving treatment (BCT) for three molecular subtypes of early stage breast cancer.
The sample studied included 596 patients with T1-2N0-1 breast cancer who received BCT. Three groups were defined by receptor status. Luminal: estrogen receptor (ER) or progesterone receptor (PR) positive; triple negative (TN): ER, PR, and epidermal growth factor receptor-2 (HER2) receptor negative; and HER2 overexpressing: ER and PR negative but HER2 receptor positive.
The number of patients in each group was 408 (68.5%), 105 (17.6%), and 83 (13.9%), respectively. The median follow-up period was 79 months. The TN and HER2 subtypes occurred in younger patients (p=0.0007) and had higher nuclear grade and poorer histologic grade (p<0.0001 and 0.0071, respectively). During the follow-up period, locoregional recurrence was detected as the first site of recurrence in 26 (6.4%), 11 (10.5%), and 9 (10.8%) patients in the luminal, TN, and HER2 subtypes, respectively (p=0.1924). Thirty-one (7.6%), 7 (6.7%), and 7 (8.4%) patients in each group had distant metastases as the first sign of recurrence (p=0.8996). Median time to locoregional and distant recurrence was shorter in the HER2 subtype (p=0.0889 and 0.0780, respectively), and the HER2 subtype was significantly associated with poor overall survival (p=0.0009).
After BCT in Korean women with early stage breast cancer, the patterns of recurrence were not different among the molecular subtypes, although the TN and HER2 subtypes were associated with younger age, higher nuclear grade, and poorer histologic grade.
Breast-conserving surgery; Breast neoplasms; erbB-2 receptor; Estrogen receptors; Progesterone receptors; Recurrence
Triple-negative breast cancers (TNBCs) and basal-like breast cancers (BLBCs) are known as poor outcome subtypes with a lack of targeted therapy. Previous studies have shown conflicting results regarding the difference of prognostic significance between TNBCs and BLBCs. In this study, we aimed to characterize the prognostic features of TNBCs, in view of BLBCs and quintuple-negative breast cancers (QNBC/5NPs).
Using tissue microarray-based immunohistochemical analysis, we categorized 951 primary breast cancers into four or five subtypes according to the expression of ER, PR, HER2, and basal markers (CK5/6, EGFR).
The results of this study showed that both TNBCs and BLBCs were associated with high histological and/or nuclear grades. When the TNBCs are divided into two subtypes by the presence of basal markers, the clinicopathologic characteristics of TNBCs were mainly maintained in the BLBCs. The 5-subgrouping was the better prediction model for both disease free and overall survival in breast cancers than the 4-subgrouping. After multivariate analysis of TNBCs, the BLBCs did not have a worse prognosis than the QNBC/5NPs. Interestingly, the patients with BLBCs showed significant adjuvant chemotherapy benefit. In addition, QNBC/5NPs comprised about 6~8% of breast cancers in publicly available breast cancer datasets
The QNBC/5NP subtype is a worse prognostic subgroup of TNBCs, especially in higher stage and this result may be related to adjuvant chemotherapy benefit of BLBCs, calling for caution in the identification of subgroups of patients for therapeutic classification.