Clinical Features of Male Breast Cancer: Experiences from Seven Institutions Over 20 Years.

PURPOSE: Breast cancer treatment has progressed significantly over the past 20 years. However, knowledge regarding male breast cancer (MBC) is sparse because of its rarity. This study is an investigation of the clinicopathologic features, treatments, and clinical outcomes of MBC. MATERIALS AND METHODS: Clinical records of 59 MBC patients diagnosed during 1995-2014 from seven institutions in Korea were reviewed retrospectively. RESULTS: Over a 20-year period, MBC patients accounted for 0.98% among total breast cancer patients, and increased every 5 years. The median age of MBC patientswas 66 years (range, 24 to 87 years). Forty-three patients (73%) complained of a palpable breast mass initially. The median symptom duration was 5 months (range, 1 to 36 months). Mastectomy was performed in 96% of the patients. The most frequent histology was infiltrating ductal carcinoma (75%). Ninety-one percent of tumors (38/43) were estrogen receptor-positive, and 28% (11/40) showed epidermal growth factor receptor 2 (HER-2) overexpression. After curative surgery, 42% of patients (19/45) received adjuvant chemotherapy; 77% (27/35) received hormone therapy. Five out of ten patients with HER-2 overexpressing tumors did not receive adjuvant anti-HER-2 therapy, while two out of four patients with HER-2 overexpressing tumors received palliative trastuzumab for recurrent and metastatic disease. Letrozole was used for one patient in the palliative setting. The median overall survival durations were 7.2 years (range, 0.6 to 17.0 years) in patients with localized disease and 2.9 years (range, 0.6 to 4.3 years) in those with recurrent or metastatic disease. CONCLUSION: Anti-HER-2 and hormonal therapy, except tamoxifen, have been underutilized in Korean MBC patients compared to female breast cancer patients. With the development of precision medicine, active treatment with targeted agents should be applied. Further investigation of the unique pathobiology of MBC is clinically warranted.

Prognostic significance of serum carcinoembryonic antigen normalization on survival in rectal cancer treated with preoperative chemoradiation.

PURPOSE: The purpose of this retrospective study was to identify factors predictive of survival in rectal cancer patients who received surgery with curative intent after preoperative chemoradiotherapy (CRT). MATERIALS AND METHODS: Between July 1996 and June 2010, 104 patients underwent surgery for rectal cancer after preoperative CRT. The median dose of radiotherapy was 50.4 Gy (range, 43.2 to 54.4 Gy) for 6 weeks. Chemotherapy was a bolus injection of 5-fluorouracil and leucovorin for the first and last week of radiotherapy (n=84, 77.1%) or capecitabine administered daily during radiotherapy (n=17, 16.3%). Low anterior resection (n=86, 82.7%) or abdominoperineal resection (n=18, 17.3%) was performed at a median 47 days from the end of radiotherapy, and four cycles of adjuvant chemotherapy was administered. The serum carcinoembryonic antigen (CEA) level was checked at initial diagnosis and just before surgery. RESULTS: After a median follow-up of 48 months (range, 9 to 174 months), 5-year disease free survival (DFS) was 74.5% and 5-year overall survival (OS) was 86.4%. Down staging of T diagnoses occurred in 32 patients (30.8%) and of N diagnoses in 40 patients (38.5%). The CEA change from initial diagnosis to pre-surgery (high-high vs. high-normal vs. normal-normal) was a statistically significant prognostic factor for DFS (p=0.012), OS (p=0.002), and distant metastasis free survival (p=0.018) in a multivariate analysis. CONCLUSION: Patients who achieve normal CEA level by the time of surgery have a more favorable outcome than those who retain a high CEA level after preoperative CRT. The normalization of CEA levels can provide important information about the prognosis in rectal cancer treatment.

Hwanggeumchal sorghum extract enhances BMP7 and GH signaling through the activation of Jak2/STAT5B in MC3T3­E1 osteoblastic cells.

Sorghum is a principal cereal food in a number of parts of the world and is critical in folk medicine in Asia and Africa. However, its effects on bone are unknown. Growth hormone (GH) is a regulator of bone growth and bone metabolism. GH activates several signaling pathways, including the Janus kinase (Jak)/signal transducer and activator of transcription (STAT) pathways, thereby regulating expression of genes, including insulin­like growth factor (IGF)­1. Bone morphogenetic proteins (BMPs) induce the differentiation of cells of the osteoblastic lineage, increasing the pool of IGF­1 target cells, the mature osteoblasts. In the present study, the effects of Hwanggeumchal sorghum extracts (HSE) on GH signaling via the Jak/STAT pathway in osteoblasts were investigated. HSE was not observed to be toxic to osteoblastic cells and increased the expression of BMP7 and GH­related proteins, including STAT5B, p­STAT5B, IGF­1 receptor (IGF-1R), growth receptor hormone (GHR) and Jak2 in MC3T3­E1 cells. In addition, HSE increased BMP7 and GHR mRNA expression in MC3T3­E1 cells. The expression of HSE­induced BMP7 and GHR was inhibited by AG490, a Jak2 kinase inhibitor. The observations indicate that HSE­induced signaling is similar to GH signaling via the GHR­Jak2 signaling axis. Using small interference RNA (siRNA) analysis, STAT5B was found to play an essential role in HSE­induced BMP7 and GH signaling in MC3T3­E1 cells. Results of the current study indicate that HSE promotes bone growth through activation of STAT5B.

Retrospective analysis of treatment outcomes for extranodal NK/T-cell lymphoma (ENKL), nasal type, stage I-IIE: single institute experience of combined modality treatment for early localized nasal extranodal NK/T-cell lymphoma (ENKL).

Extranodal natural killer/T-cell lymphoma (ENKL) is a very aggressive disease frequently involving the nasal cavity and upper aerodigestive tract. We retrospectively reviewed the treatment outcomes and treatment-associated complications of the patients with stage I-II early localized ENKL. A total of 24 patients were included. All patients were treated with combined chemoradiotherapy. Three, sixteen, and five patients were initially treated with radiation therapy, chemotherapy, and surgical procedures, respectively. Nine patients underwent hematopoietic stem cell transplantation (HSCT), and four patients administered immunotherapy with pegylated-interferon alpha. The mean observation time was 71.6 months (range, 29.7-183.6 months). Twenty patients achieved complete remission; thus, the overall response rate was 83.3 %. The 5-year overall survival (OS) and relapse-free survival (RFS) rates were 70.3 % and 62.2 %, respectively. In univariate analysis, HSCT was a significant prognostic indicator for OS and RFS. By combining HSCT, the 5-year OS and RFS rates were 100.0 % vs. 52.5 % (p = 0.018) and 88.9 % vs. 45.7 % (p = 0.045), respectively. Also, absence of B symptoms was a good prognostic factor for RFS, the 5-year RFS rate, 75.0 % vs. 25.0 % (p = 0.010), and B symptoms were significant for RFS in multivariate analysis (odds ratio = 7.4, confidence interval = 1.6~34.1, p = 0.011). However, a total of four cases of grade 3 toxicities were reported. Radiation dose range (≤4,500 vs. >4,500 cGy) was significantly correlated with late complications, as more severe complications occurred more frequently with a radiation dose >4,500 cGy (p = 0.026, in multivariate analysis). For more efficient treatment of ENKL, chemotherapy, HSCT, and/or immunotherapy can be combined with radiation therapy to prolong long-term survival and achieve good local control. Also, lower radiation dose could be administered to avoid severe late complications.

Expression, crystallization and preliminary X-ray crystallographic analysis of cystathionine γ-synthase (XometB) from Xanthomonas oryzae pv. oryzae.

Cystathionine γ-synthase (CGS) catalyzes the first step in the transsulfuration pathway leading to the formation of cystathionine from O-succinylhomoserine and L-cysteine through a γ-replacement reaction. As an antibacterial drug target against Xanthomonas oryzae pv. oryzae (Xoo), CGS from Xoo (XometB) was cloned, expressed, purified and crystallized. The XometB crystal diffracted to 2.4 Šresolution and belonged to the tetragonal space group I4(1), with unit-cell parameters a=b=165.4, c=241.7 Å. There were four protomers in the asymmetric unit, with a corresponding solvent content of 73.9%.

Prognostic significance of the lymph node ratio regarding recurrence and survival in rectal cancer patients treated with postoperative chemoradiotherapy.

BACKGROUND/AIMS: TO EVALUATE THE PROGNOSTIC IMPACT OF THE LYMPH NODE RATIO (LNR: the ratio of positive lymph nodes to the total number of lymph nodes examined) on disease recurrence and survival among rectal cancer patients who received curative surgery and postoperative chemoradiotherapy (CRT). METHODS: Between 1995 and 2008, 124 patients with pathologic T3-4 or node-positive rectal cancer underwent curative surgery and postoperative CRT. Postoperative radiotherapy was delivered at a median dose of 50.4 Gy (range, 45 to 59.4 Gy) for 6 weeks. Chemotherapy consisted of a bolus injection of 5-fluorouracil and leucovorin in the first and last week of radiotherapy (91.9%) or daily capecitabine during radiotherapy (8.1%). Further adjuvant chemotherapy was administered after chemoradiation. RESULTS: The median follow-up was 5.1 years. In the multivariate analysis, pathologic N (pN) stage and lymphovascular invasion were significantly associated with disease-free survival and disease-specific survival (p<0.05). However, when the LNR with a cutoff value of 0.2 was included as a covariate in the model, the LNR was highly significant (p<0.001), and the pN stage lost its significance (p>0.05). CONCLUSIONS: The LNR predicts recurrence and survival more accurately than pN stage. The pN stage and the LNR should be considered together when estimating the risk of disease recurrence among rectal cancer patients.

Total lymphoid irradiation based conditioning for hematopoietic stem cell transplantation in severe aplastic anemia.

PURPOSE: To retrospectively evaluate the outcome and toxicity of total lymphoid irradiation (TLI) based conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) patients who experienced an engraftment failure from prior HSCT or were heavily transfused. MATERIALS AND METHODS: Between 1995 and 2006, 20 SAA patients received TLI for conditioning of HSCT. All patients were multi-transfused or had long duration of disease. Fifteen (75%) patients had graft failure from prior HSCT. In 18 (90%) patients, the donors were human leukocyte antigen identical siblings. The stem cell source was the peripheral blood stem cell in 15 (75%) patients. The conditioning regimen was composed of antithymocyte globulin plus TLI with a median dose of 750 cGy in 1 fraction. The graft-versus-host disease (GVHD) prophylaxis used cyclosporine with methotrexate. RESULTS: With a median follow-up of 10.8 years, graft failures developed in 6 patients. Among them, 3 patients received their third HSCT to be engrafted finally. The Kaplan-Meier overall survival rate was 85.0% and 83.1% at 5 and 10 years, respectively. The incidence of acute and chronic GVHD was 20% and 20%, respectively. None of the patients have developed a malignancy after HSCT. CONCLUSION: In our study, TLI based conditioning in allogeneic HSCT was feasible with acceptable rates of GVHD in SAA patients who experienced graft failure from prior HSCT or was at a high risk of graft rejection. We achieved relatively better results of engraftment and survival with a long term follow-up.

The prognostic significance of the lymph node ratio in axillary lymph node positive breast cancer.

PURPOSE: This study evaluated the prognostic impact of the lymph node ratio (LNR; i.e., the ratio of positive to dissected lymph nodes) on recurrence and survival in breast cancer patients with positive axillary lymph nodes (LNs). METHODS: The study cohort was comprised of 330 breast cancer patients with positive axillary nodes who received postoperative radiotherapy between 1987 and 2004. Ten-year Kaplan-Meier locoregional failure, distant metastasis, disease-free survival (DFS) and disease-specific survival (DSS) rates were compared using Kaplan-Meier curves. The prognostic significance of the LNR was evaluated by multivariate analysis. RESULTS: Median follow-up was 7.5 years. By minimum p-value approach, 0.25 and 0.55 were the cutoff values of LNR at which most significant difference in DFS and DSS was observed. The DFS and DSS rates correlated significantly with tumor size, pN classification, LNR, histologic grade, lymphovascular invasion, the status of estrogen receptor and progesterone receptor. The LNR based classification yielded a statistically larger separation of the DFS curves than pN classification. In multivariate analysis, histologic grade and pN classification were significant prognostic factors for DFS and DSS. However, when the LNR was included as a covariate in the model, the LNR was highly significant (p<0.0001), and pN classification was not statistically significant (p>0.05). CONCLUSION: The LNR predicts recurrence and survival more accurately than pN classification in our study. The pN classification and LNR should be considered together in risk estimates for axillary LNs positive breast cancer patients.

Hepatocellular carcinoma with portal vein tumor thrombosis: Improved treatment outcomes with external beam radiation therapy.

The treatment of advanced hepatocellular carcinoma (HCC) associated with portal vein tumor thrombosis (PVTT) is very challenging because of HCC's grave prognosis. Despite many efforts to improve the treatment results, patient survival has been limited to several months. In this situation, radiotherapy has been considered as an alternative treatment modality because of the growth of knowledge about the radiotolerance of normal tissue and the advances of radiotherapy techniques such as three dimensional conformal radiotherapy, intensity modulated radiotherapy, stereotactic body radiotherapy and proton therapy. More restoration of the liver function and longer survival of the patients can be achieved by the better response after radiotherapy. However, considering the high risk of intrahepatic advanced tumor or extrahepatic dissemination by PVTT at disease presentation, a combination of radiation therapy and systemic agents will be desirable. Therefore, performing prospective randomized clinical trials is important to assess the benefits of radiotherapy and to develop combination treatment strategies.

Fractionated stereotactic radiotherapy as reirradiation for locally recurrent head and neck cancer.

PURPOSE: We report early preliminary experience with CyberKnife radiosurgery (RS) as salvage treatment for locally recurrent head and neck cancer (HNC). METHODS AND MATERIALS: Between March 2004 and August 2006, 36 patients (44 sites) were treated with CyberKnife RS as reirradiation for locally recurrent HNC. Treatment sites were as follows: nasopharynx (8), maxillary sinus (8), neck lymph nodes (8), skull base (7), nasal cavity (4), retropharyngeal lymph nodes (3), orbit (2), and others (4). Total doses administered were 18-40 Gy (median, 30 Gy) in 3 to 5 fractions to the 65%-85% isodose line for 3-5 consecutive days. Previous external radiation dose ranged from 39.6 to 134.4 Gy (median, 70.2 Gy). Gross tumor volume ranged from 0.2 to 114.9 cm(3) (median, 22.6 cm(3)). Median follow-up was 17.3 months. RESULTS: Thirty-five of 44 sites were evaluated for response. Fifteen (42.9%) sites achieved complete response, 13 sites (37.1%) achieved a partial response, 3 (8.6%) sites maintained stable disease, and 4 sites (11.4%) showed tumor progression. Grade III acute complications were noted in 13 patients. Late complications were observed in three patients (1 bone necrosis, 2 soft tissue necrosis) during follow-up. CONCLUSION: These preliminary results suggest that fractionated stereotactic radiosurgery is an effective treatment modality as a salvage treatment with good short-term local control. The early overall response rate is encouraging. However, more experience and a longer follow-up are necessary to determine the role of fractionated stereotactic radiosurgery as a salvage treatment of locally recurrent HNC and to define long-term complications.

Radiation therapy combined with (or without) cisplatin-based chemotherapy for patients with nasopharyngeal cancer: 15-years experience of a single institution in Korea.

PURPOSE: This retrospective study was carried out to evaluate the efficacy and toxicity of radiation therapy (RT) with/without cisplatin-based chemotherapy in nasopharyngeal cancer (NPC). MATERIALS AND METHODS: One hundred forty six patients with NPC received curative RT and/or cisplatin-based chemotherapy. Thirty-nine patients were treated with induction chemotherapy (IC), including cisplatin and 5-fluorouracil followed by RT. Another 63 patients were treated with concurrent chemoradiotherapy (CCRT) using cisplatin, and 22 patients were treated with IC followed by CCRT. The remaining 22 patients were treated with RT alone. RESULTS: One hundred four (80.0%) patients achieved complete response (CR), and 23 (17.7%) patients achieved partial response (PR). The patterns of failure were: locoregional recurrences in 21.2% and distant metastases in 17.1%. Five-year overall survival (OS) and progression free survival (PFS) were 50.7% and 45.0%, respectively. Multivariate Cox stepwise regression analysis revealed CR to chemoradiotherapy to be a powerful prognostic factor for OS. CR to chemoradiotherapy and completion of radiation according to the time schedule were favorable prognostic factors for PFS. A comparison of each treatment group (IC --> RT vs. CCRT vs. IC --> CCRT vs. RT alone) revealed no significant differences in the OS or PFS. However, subgroup analysis showed significant differences in both OS and DFS in favor of the combined chemoradiotherapy group compared with RT alone, for stage IV and T3-4 tumors. Grade 3-4 toxicities were more common in the combined chemoradiotherapy arm, particularly in the CCRT group. CONCLUSIONS: This study was limited in that it was a retrospective study, much time was required to collect patients, and there were imbalances in the number of patients in each treatment group. Combined chemoradiotherapy remarkably prolonged the OS and PFS in subgroup patients with stage IV or T3-4 NPC.

Neovastat (AE-941) inhibits the airway inflammation via VEGF and HIF-2 alpha suppression.

Vascular endothelial growth factor (VEGF) contributes to airway inflammation and angiogenesis in asthma. Hypoxia inducible factor (HIF), the most potent regulator of VEGF, is a heterodimer of a constitutively expressed beta subunit and an oxygen-regulated alpha subunit (HIF-alpha). Three HIF-alpha isoforms have been described, of which HIF-2 alpha are abundantly expressed in lung tissue. Neovastat is a naturally occurring inhibitor of angiogenesis derived from marine cartilage. We previously reported that Neovastat can inhibit the airway inflammation in asthma. In this study, we hypothesized that the anti-inflammatory effect of Neovastat is mediated with inhibition of VEGF and HIF-2 alpha. BALB/c mice were immunized subcutaneously and challenged with inhaled ovalbumin (OVA). Neovastat was administrated by gavage three times with 12-h interval, beginning at 30 min before OVA inhalation. VEGF concentration in bronchoalveolar lavage fluid was measured by ELISA. We evaluate the expression of VEGF and HIF-2 alpha in lung tissue by immunohistochemistry. Mice treated with Neovastat had significantly reduced inflammatory cell count in BAL fluid compared with untreated asthmatic mice. Furthermore, Mice treated with Neovastat showed significantly reduced VEGF and HIF-2 alpha expression on lung tissue. These results suggest that anti-inflammatory effects of Neovastat could be linked to inhibition of VEGF and HIF-2 alpha.

Characterization, cloning and expression of the ferritin gene from the Korean polychaete, Periserrula leucophryna.

Ferritin is a major eukaryotic protein and in humans is the protein of iron storage. A partial gene fragment of ferritin (255 bp) taken from the total RNA of Periserrula leucophryna, was amplified by RT-PCR using oligonucleotide primers designed from the conserved metal binding domain of eukaryotic ferritin and confirmed by DNA sequencing. Using the 32P-labeled partial ferritin cDNA fragment, 28 different clones were obtained by the screening of the P. leucophryna cDNA library prepared in the Uni-ZAP XR vector, sequenced and characterized. The longest clone was named the PLF (Periserrula leucophryna ferritin) gene and the nucleotide and amino acid sequences of this novel gene were deposited in the GenBank databases with accession numbers DQ207752 and ABA55730, respectively. The entire cDNA of PLF clone was 1109 bp (CDS: 129-653), including a coding nucleotide sequence of 525 bp, a 5'-untranslated region of 128 bp, and a 3'-noncoding region of 456 bp. The 5'-UTR contains a putative iron responsive element (IRE) sequence. Ferritin has an open reading frame encoding a polypeptide of 174 amino acids including a hydrophobic signal peptide of 17 amino acids. The predicted molecular weights of the immature and mature ferritin were calculated to be 20.3 kDa and 18.2 kDa, respectively. The region encoding the mature ferritin was subcloned into the pT7-7 expression vector after PCR amplification using the designed primers and included the initiation and termination codons; the recombinant clones were expressed in E. coli BL21(DE3) or E. coli BL21(DE3)pLysE. SDS-PAGE and western blot analysis showed that a ferritin of approximately 18 kDa (mature form) was produced and that by iron staining in native PAGE, it is likely that the recombinant ferritin is correctly folded and assembled into a homopolymer composed of a single subunit.

The effect of simulation on recurrence after breast-conserving surgery and radiotherapy: preliminary results.

PURPOSE: To evaluate the effect of the simulation method on recurrence among the patients who received radiotherapy after breast-conserving surgery (BCS) for early breast carcinoma. MATERIALS AND METHODS: Between 1995 and 2000, 70 patients with stage I-II breast carcinoma underwent breast-conserving surgery and adjuvant radiotherapy. Twenty nine patients (41.4%) were simulated with the 2D contour-based method (September 1995 to August 1997) and 41 patients (58.6%) were simulated with the 3D CT-based method (September 1997 to February 2000). To analyze the effect of the simulation method, the patient and treatment characteristics were compared. RESULTS: The characteristics were similar for the patients between the 2D contour-based simulation group and the 3D CT-based simulation group. During a median follow-up period of 75 months, 4 (13.8%) of 29 patients who were treated with 2D simulation and 1 (2.4%) of 41 patients who were treated with 3D simulation group developed treatment failure. The five-year survival rates were 89.2% and 95.1% between the 2D and 3D simulation groups (p=0.196). The five-year disease free survival (DFS) rates were 86.2% and 97.5% between the 2D and 3D simulation groups (p=0.0636). On univariate analysis, age > 40 (p= 0.0226) and the number of dissected axillary lymph node >or= 10 (p=0.0435) were independent predictors of improved 5-year DFS. CONCLUSIONS: Although our data showed marginal significance for the DFS between the two groups, it is insufficient, due to the small number of patients in our study, to prove whether 3D CT-based simulation might improve the DFS and reduce the risk of recurrence when compared with 2D contour-based simulation. Further study is needed with a larger group of patients.

Neovastat (AE-941) inhibits the airway inflammation and hyperresponsiveness in a murine model of asthma.

Matrix metalloproteinase (MMP)-9 plays an important role in the pathogenesis of bronchial asthma. Neovastat, having significant antitumor and antimetastatic properties, is classified as a naturally occurring multifunctional antiangiogenic agent. We evaluated the therapeutic effect of Neovastat on airway inflammation in a mouse model of asthma. BALB/c mice were immunized subcutaneously with ovalbumin (OVA) on days 0, 7, 14, and 21 and challenged with inhaled OVA on days 26, 29, and 31. Neovastat was administrated by gavage (5 mg/kg body weight) three times with 12 h intervals, beginning 30 min before OVA inhalation. On day 32, mice were challenged with inhaled methacholine, and enhanced pause (Penh) was measured as an index of airway hyperresponsiveness. The severity of airway inflammation was determined by differential cell count of bronchoalveolar lavage (BAL) fluid. The MMP-9 concentration in BAL fluid samples was measured by ELISA, and MMP-9 activity was measured by zymography. The untreated asthma group showed an increased inflammatory cell count in BAL fluid and Penh value compared with the normal control group. Mice treated with Neovastat had significantly reduced Penh values and inflammatory cell counts in BAL fluid compared with untreated asthmatic mice. Furthermore, mice treated with Neovastat showed significantly reduced MMP-9 concentrations and activity in BAL fluid. These results demonstrate that Neovastat might have new therapeutic potential for airway asthmatic inflammation.

Combined effect of heptaplatin and ionizing radiation on human squamous carcinoma cell lines.

Heptaplatin, cis-malonato [(4R,5R)-4,5-bis (amino-methyl)-2-isopropyl-1,3-dioxolane] platinum(II) (SKI-2053R, Sunpla) is a new platinum derivative with anti-tumor activity comparable to cisplatin on various cancer cell lines. Preclinical studies suggest that it is less nephrotoxic than cisplatin. This study was undertaken to examine the combined effect of heptaplatin and ionizing radiation on two established human squamous carcinoma cell lines (NCI-H520, SQ20B). The cytotoxic activity of heptaplatin was concentration-dependent in both cell lines. When low dose heptaplatin was combined with high dose ionizing radiation, there was an additive cytotoxic effect on NCI-H520 cells (P < 0.05), while a moderate dose of heptaplatin and a low dose of ionizing radiation had an additive cytotoxic effect on the growth of SQ20B cells (P < 0.05). FACS analysis and DAPI staining showed that their additive cytotoxic effects were correlated with the induction of apoptosis. Further studies are warranted using heptaplatin and ionizing radiation in squamous cell carcinoma as a substitute for cisplatin.

Clinical experience of patients with ductal carcinoma in situ of the breast treated with breast-conserving surgery plus radiotherapy: a preliminary report.

PURPOSE: Breast-conserving therapy (BCT) is a practical alternative to mastectomy for treating ductal carcinoma in situ (DCIS). We reviewed our experience for treating patients with DCIS of the breast to evaluate the outcome after performing breast-conserving surgery plus radiotherapy (BCS-RT). MATERIALS AND METHODS: Between January 1983 and December 2002, 25 patients with clinically or mammographically detected DCIS were treated by BCS-RT. One patient was diagnosed with bilateral DCIS. Thirteen cases (50%) had symptomatic lesions at presentation. All 26 cases of 25 patients underwent BCS such as lumpectomy, partial mastectomy or quadrantectomy. All of them received whole breast irradiation to a median dose of 50.4 Gy. Twenty-four cases (92.3%) received a boost to the tumor bed for a median total dose of 59.4 Gy. The median follow up period was 67 months (range: 38 to 149 months). RESULTS: Two cases (7.7%) experienced ipsilateral breast tumor recurrence (IBTR) after BCS-RT. The histology results at the time of IBTR showed invasive ductal carcinoma (IDC), and the median time to IBTR was 25.5 months. On the univariate analysis, there were no significant factors associated with IBTR in the DCIS patients. The three-year local recurrence free survival rate was 96.0% and the overall survival rate was 96.3%. CONCLUSION: After the treatment for DCIS, the IBTR rate in our study was similar to other previous studies. Considering that we included patients who had many symptomatic lesions, close or positive margins and less that complete early data, our result is comparable to the previous studies. We could not find the prognostic significant factors associated with IBTR after BCS-RT. A longer follow up period with more patients would be required to evaluate the role of any predictive factors and to confirm these short-term results.

The role of radiation therapy for the extramammary paget's disease of the vulva ; experience of 3 cases.

We have experienced three cases of extramammary Paget's disease (EMPD) of the vulva that received radiation therapy (RT). Here, we analyze the efficacy of RT and include a literature survey.Three patients with EMPD of the vulva were treated with curative RT between 1993 and 1998. One of the patients had associated underlying adenocarcinoma of the vulva. The total doses of radiation administered were 54~78 Gy/6~8 weeks. Radiation fields encompassed 2 to 3 cm outer margins free from all visible disease including or not including the inguinal area using a 9 MeV electron or a 6 MV photon beam. Follow-up durations after radiotherapy were 0.6~11 years. Complete response was obtained in all three patients. Marginal failure occurred in one patient, and another patient with underlying adenocarcinoma treated by vulvectomy with bilateral inguinal lymph node dissection followed by external RT showed no relapse. Radiation induced side effects were transient acute confluent wet desquamation in the treated area resulting in mild late atrophic skin changes.Although surgery is currently considered the preferred primary treatment for EMPD, it has a high relapse rate due to the multifocal nature of the disease. We conclude that RT is of benefit in some selected cases of EMPD.