The ham-5, rcm-1 and rco-1 genes regulate hyphal fusion in Neurospora crassa

Mutants of Neurospora crassa unable to participate in vegetative hyphal fusion (anastomosis) were isolated and characterized. From this analysis, three genes, rcm-1, rco-1 and ham-5, were identified and shown to be required for hyphal fusion. The rcm-1 and rco-1 genes are homologues of the Saccharomyces cerevisiae SSN6 and TUP1 genes, which encode a dimeric transcription factor in yeast. We demonstrate that in N. crassa the rcm-1 and rco-1 genes are required for hyphal fusion and normal hyphal morphology, and influence both asexual and sexual development. The ham-5 gene encodes a 1686 amino acid protein with two putative WD40 domains, which might participate in protein–protein interactions. ham-5 deletion mutants had a reduced rate of hyphal extension and altered hyphal morphology, and were unable to produce the conidial anastomosis tubes that are required for hyphal fusion during colony initiation

Three-year analysis of treatment efficacy, cosmesis, and toxicity by the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial in patients treated with accelerated partial breast irradiation (APBI).

BACKGROUND: This report presents 3 years of data on treatment efficacy, cosmetic results, and toxicities for patients enrolled on the American Society of Breast Surgeons MammoSite (Cytyc, Bedford, Mass) Breast Brachytherapy Registry Trial. METHODS: A total of 1440 patients (1449 cases) with early stage breast cancer who were undergoing breast-conserving therapy were treated with the MammoSite device to deliver accelerated partial breast irradiation (APBI) (34 Gy in 3.4 Gy fractions). Of these, 1255 (87%) cases had invasive breast cancer (IBC; median size = 10 mm), and 194 (13%) cases had ductal carcinoma in situ (DCIS; median size = 8 mm). Median follow-up was 30.1 months. RESULTS: Twenty-three (1.6%) cases developed an ipsilateral breast tumor recurrence (IBTR) for a 2-year actuarial rate of 1.04% (1.11% for IBC and 0.59% for DCIS). No variables were associated with IBTR. Six (0.4%) patients developed an axillary failure. The percentages of breasts with good to excellent cosmetic results at 12 (n = 980), 24 (n = 752), 36 (n = 403), and 48 months (n = 67 cases) were 95%, 94%, 93%, and 93%, respectively. Breast seromas were reported in 23.9% of cases (30% in open-cavity implants and 19% in closed-cavity implants). Symptomatic seromas occurred in 10.6% of cases, and 1.5% of cases developed fat necrosis. A subset analysis of the first 400 consecutive cases enrolled was performed (352 with IBC, 48 DCIS). With a median follow-up of 37.5 months, the 3-year actuarial rate of IBTR was 1.79%. CONCLUSIONS: Treatment efficacy, cosmesis, and toxicity 3 years after treatment with APBI using the MammoSite device are good and similar to those reported with other forms of APBI with similar follow-up

Four-year clinical update from the American Society of Breast Surgeons MammoSite brachytherapy trial.

BACKGROUND: We present a 4-year update on the efficacy, cosmetic results, and complications of MammoSite breast brachytherapy in patients enrolled in the American Society of Breast Surgeons registry trial. METHODS: A total of 1,449 breasts in 1,440 patients with early stage breast cancer undergoing breast-conserving therapy were treated with adjuvant, accelerated partial breast irradiation (APBI) (34 Gy in 3.4-Gy fractions) delivered with the MammoSite device. The median follow-up period for the entire group was 36.1 months. RESULTS: The 3-year actuarial rate of ipsilateral breast tumor recurrence was 2.15%. The 3-year actuarial rate of axillary recurrence was .36%. Complication rates were as follows: infection, 9.5%; seroma, 26.8% (symptomatic seroma, 12.7%); and fat necrosis, 2.0%. The percentages of breasts with good or excellent cosmetic results were as follows: 12 months, 95%; 24 months, 94%; 36 months, 94%; and 48 months, 91%. CONCLUSIONS: Locoregional control, complications, and cosmetic outcomes from MammoSite APBI at the 4-year update are acceptable and similar to results seen with other forms of APBI

Local control, toxicity, and cosmesis in women \u3e70 years enrolled in the American Society of Breast Surgeons accelerated partial breast irradiation registry trial

Purpose: The American Society of Breast Surgeons enrolled women in a registry trial to prospectively study patients treated with the MammoSite Radiation Therapy System breast brachytherapy device. The present report examined the outcomes in women aged \u3e70 years enrolled in the trial. Methods and Materials: A total of 1,449 primary early stage breast cancers were treated in 1,440 women. Of these, 537 occurred in women \u3e70 years old. Fisher\u27s exact test was performed to correlate age (≤70 vs. \u3e70 years) with toxicity and with cosmesis. The association of age with local recurrence (LR) failure times was investigated by fitting a parametric model. Results: Older women were less likely to develop telangiectasias than younger women (7.9% vs. 12.4%, p = 0.0083). The incidence of other toxicities was similar. Cosmesis was good or excellent in 92% of the women \u3e70 years old. No significant difference was found in LR as a function of age. The 5-year actuarial LR rate with invasive disease for the older vs. younger population was 2.79% and 2.92%, respectively (p = 0.5780). In women \u3e70 years with hormone-sensitive tumors ≤2 cm who received hormonal therapy (n = 195), the 5-year actuarial rate of LR, overall survival, disease-free survival, and cause-specific survival was 2.06%, 89.3%, 87%, and 97.5%, respectively. These outcomes were similar in women who did not receive hormonal therapy. Women with small, estrogen receptor-negative disease had worse LR, overall survival, and disease-free survival compared with receptor-positive patients. Conclusions: Accelerated partial breast irradiation with the MammoSite radiation therapy system resulted in low toxicity and produced similar cosmesis and local control at 5 years in women \u3e70 years compared with younger women. This treatment should be considered as an alternative to omitting adjuvant radiotherapy for older women with small-volume, early-stage breast cancer. © 2012 Elsevier Inc

Initial outcomes for patients treated on the American Society of Breast Surgeons MammoSite clinical trial for ductal carcinoma-in-situ of the breast.

BACKGROUND: The MammoSite device was designed as a breast brachytherapy applicator and is currently used to deliver accelerated partial breast irradiation (APBI). We hypothesized that APBI delivered with the MammoSite device would be well tolerated and be associated with a good cosmetic outcome in patients with ductal carcinoma-in-situ (DCIS). METHODS: From 2002 to 2004, 191 patients with DCIS were enrolled in a registry trial to assess the MammoSite applicator. Fifteen patients were excluded from analysis because of device- or patient-related factors; 7 patients were excluded after receiving a radiotherapy boost, thus leaving 169 patients available for study. Follow-up information was available for 158 patients. The average length of follow-up was 7.35 months. Forty-three patients had at least 1 year of follow-up. RESULTS: Skin spacing for the MammoSite applicator was as follows: \u3c 5 mm, 3 patients (1.78%); 5 to 7 mm, 18 patients (10.65%); and \u3e or = 7 mm, 148 patients (87.57%). Patients with a device-to-skin distance of \u3e or = 7 mm had the best cosmetic result. Patients with a device-to-skin distance of \u3e or = 7 mm also had a lower incidence of radiation dermatitis. Data on 43 patients who were followed up for at least 1 year confirmed these findings. Additional adverse events were primarily related to skin changes, with breast infections occurring in five patients (3.16%). No patient in the study has experienced a recurrence. CONCLUSIONS: APBI delivered via MammoSite is well tolerated in patients with DCIS, and the lowest toxicity was obtained in patients with the greatest device-to-skin distance. Long-term follow-up data regarding patient satisfaction, cosmesis, and efficacy are needed and will be determined from a recently opened large randomized study

First analysis of patient demographics, technical reproducibility, cosmesis, and early toxicity: results of the American Society of Breast Surgeons MammoSite breast brachytherapy trial.

BACKGROUND: Eighty-seven institutions participated in a Registry Trial that was designed to collect data on the clinical use of the MammoSite breast brachytherapy catheter for delivering breast irradiation. Patient demographics, technical reproducibility, cosmesis, and early toxicity were evaluated. METHODS: From May 4, 2002 through July 30, 2004, 1419 patients with Stage 0, I, or II breast carcinoma who were undergoing breast-conserving therapy were enrolled on the trial. The device was placed in 1403 of these patients. The 1237 patients (87% of enrolled patients) who received accelerated partial breast irradiation (APBI) (34 grays prescribed to 1.0 cm in 10 fractions; 95% of patients who received APBI) constituted the study population; 86% of those patients (1068) had Stages I-II breast carcinoma (median tumor size, 10 mm), and 14% of those patients (169) had Stage 0 breast carcinoma. Ninety-one percent of the patients with invasive carcinoma (977 of 1068 patients) had negative lymph node status, and 99% of all patients had negative margins. The median patient age was 65 years. Systemic chemotherapy alone was administered to 79 patients with invasive carcinoma (7%), hormone therapy was administered to 501 patients (45%), and both were administered to 39 patients (4%). The median follow-up was 5 months. RESULTS: Five hundred fifty-four catheters (45%) were placed with an open cavity at the time of lumpectomy, and 683 catheters (55%) were placed with a closed cavity after lumpectomy. Skin spacing ranged from 2 mm to 75 mm (median, 10 mm). In 89% of patients, there was a minimum balloon-to-skin distance of 7 mm (2% of patients had distances \u3c 5 mm). In terms of cosmetic assessment, 95% of patients (1030 of 1084 patients) who had a cosmetic assessment had a good/excellent result (last follow-up visit). Cosmetic results at 12 months were good/excellent in 92% of 248 evaluable patients. The median skin spacing (\u3e or = 7 mm vs. \u3c 7 mm) was associated significantly with a good/excellent cosmetic result (96.1% vs. 86.8%; P = 0.0001) overall and at 6 months (P = 0.006). Increasing skin spacing was associated with a good/excellent cosmetic result as a continuous variable (P \u3c 0.0001). In total, 92 of 1140 evaluable patients (8.1%) developed an infection in the breast, which was device-related in 5.3% of patients (60 of 1140 patients). Good/excellent cosmetic results were noted in 86% of these patients (last follow-up visit). Fifteen of 442 evaluable patients (3.4%) developed a radiation recall reaction. Good/excellent cosmetic results were noted in 93% of these patients at their last follow-up visit. One local recurrence (0.1%) was reported (new primary carcinoma). CONCLUSIONS: Clinical evaluation of the ability of the MammoSite breast brachytherapy catheter to deliver APBI demonstrated acceptable technical reproducibility between multiple institutions and use in appropriate groups of patients. Cosmetic results at 12 months (92% good/excellent) were comparable to those reported with whole-breast RT. Early toxicity rates (infections, radiation recall) appeared to be acceptable