Performance of a novel spectroscopy-based tool for adjuvant therapy decision-making in hormone receptor-positive breast cancer: a validation study.

PURPOSE: Digistain Index (DI), measured using an inexpensive mid-infrared spectrometer, reflects the level of aneuploidy in unstained tissue sections and correlates with tumor grade. We investigated whether incorporating DI with other clinicopathological variables could predict outcomes in patients with early breast cancer. METHODS: DI was calculated in 801 patients with hormone receptor-positive, HER2-negative primary breast cancer and ≤ 3 positive lymph nodes. All patients were treated with systemic endocrine therapy and no chemotherapy. Multivariable proportional hazards modeling was used to incorporate DI with clinicopathological variables to generate the Digistain Prognostic Score (DPS). DPS was assessed for prediction of 5- and 10-year outcomes (recurrence, recurrence-free survival [RFS] and overall survival [OS]) using receiver operating characteristics and Cox proportional hazards regression models. Kaplan-Meier analysis evaluated the ability of DPS to stratify risk. RESULTS: DPS was consistently highly accurate and had negative predictive values for all three outcomes, ranging from 0.96 to 0.99 at 5 years and 0.84 to 0.95 at 10 years. DPS demonstrated statistically significant prognostic ability with significant hazard ratios (95% CI) for low- versus high-risk classification for RFS, recurrence and OS (1.80 [CI 1.31-2.48], 1.83 [1.32-2.52] and 1.77 [1.28-2.43], respectively; all P < 0.001). CONCLUSION: DPS showed high accuracy and predictive performance, was able to stratify patients into low or high-risk, and considering its cost and rapidity, has the potential to offer clinical utility.

Surgical perspectives from a prospective, nonrandomized, multicenter study of breast conserving surgery and adjuvant electronic brachytherapy for the treatment of breast cancer.

BACKGROUND: Accelerated partial breast irradiation (APBI) may be used to deliver radiation to the tumor bed post-lumpectomy in eligible patients with breast cancer. Patient and tumor characteristics as well as the lumpectomy technique can influence patient eligibility for APBI. This report describes a lumpectomy procedure and examines patient, tumor, and surgical characteristics from a prospective, multicenter study of electronic brachytherapy. METHODS: The study enrolled 65 patients of age 45-84 years with ductal carcinoma or ductal carcinoma in situ, and 44 patients, who met the inclusion and exclusion criteria, were treated with APBI using the Axxent® electronic brachytherapy system following lumpectomy. The prescription dose was 34 Gy in 10 fractions over 5 days. RESULTS: The lumpectomy technique as described herein varied by site and patient characteristics. The balloon applicator was implanted by the surgeon (91%) or a radiation oncologist (9%) during or up to 61 days post-lumpectomy (mean 22 days). A lateral approach was most commonly used (59%) for insertion of the applicator followed by an incision site approach in 27% of cases, a medial approach in 5%, and an inferior approach in 7%. A trocar was used during applicator insertion in 27% of cases. Local anesthetic, sedation, both or neither were administered in 45%, 2%, 41% and 11% of cases, respectively, during applicator placement. The prescription dose was delivered in 42 of 44 treated patients. CONCLUSIONS: Early stage breast cancer can be treated with breast conserving surgery and APBI using electronic brachytherapy. Treatment was well tolerated, and these early outcomes were similar to the early outcomes with iridium-based balloon brachytherapy.

Twelve-month follow-up results of a trial utilizing Axxent electronic brachytherapy to deliver intraoperative radiation therapy for early-stage breast cancer.

BACKGROUND: Accelerated partial breast irradiation (APBI) is emerging as a valid alternative to whole-breast radiation therapy (WBRT) in breast-conserving therapy (BCT) for early-stage breast cancer. Axxent electronic brachytherapy (EBX) is a form of portable, balloon-based APBI that utilizes an electronic source of kilovoltage irradiation delivery with minimal shielding requirements. As such, EBX becomes a logical and convenient modality for delivery of intraoperative radiation therapy (IORT). We report 1-year results and clinical outcomes of a trial that utilizes EBX to deliver IORT for patients with early-stage breast cancer. METHODS: Eleven patients were enrolled on an institutional review board (IRB)-approved protocol. Inclusion criteria were patient age >45 years, unifocal tumors with infiltrating ductal or ductal carcinoma in situ (DCIS) histology, tumors ≤3 cm, and uninvolved lymph nodes. Preloaded radiation plans were used to deliver radiation prescription dose of 20 Gy to the balloon surface. RESULTS: The mean time for radiation delivery was 22 min; the total mean procedure time was 1 h 39 min. All margins of excision were negative on final pathology. At mean follow-up of 12 months, overall cosmesis was excellent in 10 of 11 patients. No infection, fat necrosis, desquamation, rib fracture or cancer recurrence has been observed. There was no evidence of fibrosis at last follow-up. CONCLUSION: IORT utilizing EBX is emerging as a feasible, well-tolerated alternative to postsurgical APBI. Further research and longer follow-up data on EBX and other IORT methods are needed to establish the clinical efficacy and safety of this treatment.

Intraoperative radiation therapy in the treatment of early-stage breast cancer utilizing xoft axxent electronic brachytherapy.

BACKGROUND: In an effort to overcome the barriers to BCT, alternative methods of delivering radiation therapy have been explored. APBI allows the radiation treatment to be accomplished in one week or less. XB is a form of balloon-based APBI that uses an electronic source generated by a mobile controller unit. Investigators have also explored IORT treatment that delivers a single fraction of radiation in the operating suite at the time of surgery. METHODS: We report on the first patient treated with XB to deliver IORT. RESULTS: IORT treatment utilizing XB is feasible and can be accomplished with a total procedure time of approximately 2 hours. CONCLUSION: Further research on XB and other methods of IORT is needed to establish clinical efficacy and safety for patients with early-stage breast cancer.

The surgeon's role in breast brachytherapy.

Although two-thirds of invasive breast cancers and half of non-invasive breast cancers are amenable to lumpectomy, only about 70% of such patients choose breast conservation. Of that group, up to one-third do not follow-up with radiation therapy despite it being clinically indicated. The reasons include the patient's and surgeon's attitude toward breast conservation as well as the inconvenience and distance of a suitable radiation facility. The advent of shorter courses of radiation therapy may encourage more patients to seek adjuvant therapy. An increasingly popular and more convenient alternative to traditional whole-breast radiation therapy in patients with early-stage breast cancer is accelerated partial breast irradiation (APBI), for which the American Society of Breast Surgeons and the American Brachytherapy Society have promulgated guidelines for candidate selection. Although several methods are emerging, the most widely used brachytherapy technique utilizes the MammoSite single-catheter balloon brachytherapy device. In a best practices symposium convened in 2006, breast surgeons from academic and community practices with extensive experience in balloon brachytherapy developed general guidelines for integrating APBI into a breast surgical practice. Important considerations include patient age, histology, tumor location and size, and breast size. Thoughtful lumpectomy planning is essential to optimize balloon placement. Real-time sonographic guidance is essential as the surgeon should attend closely to volume excised and cavity shape. A cavity evaluation device can act as a place holder while patient suitability for APBI is considered. Many breast surgeons expert in this procedure insert the balloon catheter in the office either through a de novo skin entrance site removed from the lumpectomy incision or through the original incision. Optimally, insertion occurs within 2-3 weeks after lumpectomy. Close and continual communication with the radiation oncologist is essential to assure optimal outcomes. In this review, several key aspects of a successful APBI program from a surgeon's perspective as well as a consensus panel from a best practices symposium on the topic herein are highlighted.

A dosimetric comparison of MammoSite high-dose-rate brachytherapy and Xoft Axxent electronic brachytherapy.

PURPOSE: Over 20,000 patients have been treated with partial breast irradiation (PBI) using the MammoSite balloon brachytherapy applicator (IBB). Recently, a new form of balloon-based PBI, Xoft Axxent electronic brachytherapy (KVB), which uses a 50-kV x-ray source, has been introduced. This analysis was undertaken to dosimetrically compare the results of treatment using these two methods of PBI. METHODS AND MATERIALS: The study population consisted of 15 patients previously treated with IBB. The planning CT scans from these 15 patients were used to construct hypothetical treatment plans using the source characteristics of the KVB device. The plans were then compared using the dosimetric parameters discussed below. RESULTS: The mean %V(90) was 99.6% vs. 99.0% (p=nonsignificant [ns]), the mean %V(100) was 96.5% vs. 96.5%, the mean %V(150) was 41.8% vs. 59.4% (p<0.05), the mean %V(200) was 11.3% vs. 32.0% (p<0.05), and the mean %V(300) was 0.4% vs. 6.7% (p<0.05) for the IBB and KVB methods, respectively. The mean ipsilateral breast %V(50) was 19.8% vs. 13.0% (p<0.05), the mean ipsilateral lung %V(30) was 3.7% vs. 1.1% (p<0.05), and the mean heart %V(5) was 59.2% vs. 9.4% (p<0.05) for the IBB and KVB methods, respectively. CONCLUSIONS: The IBB and KVB methods of PBI offer comparable target volume coverage; however, the KVB method is associated with an increased volume of breast tissue in the high-dose regions and a decreased dose to the adjacent normal tissues.

Prospective randomized study comparing cryo-assisted and needle-wire localization of ultrasound-visible breast tumors.

BACKGROUND: This study compared the surgical results of 2 localization methods-cryo-assisted localization (CAL) and needle-wire localization (NWL)-in patients undergoing breast lumpectomy for breast cancer. METHODS: A total of 310 patients were treated in an institutional review board-approved study with 18 surgeons at 17 sites. Patients were randomized 2:1 to undergo either intraoperative CAL or NWL. A cryoprobe was inserted under ultrasound guidance in the operating room and an ice ball created an 8- to 10-mm margin around the lesion. The palpable ice ball then was dissected. NWL was placed according to institutional practice and resection was performed in a standard fashion. Surgical margins, complications, re-excisions, tissue volume, procedure times, ease of localization, specimen quality, and patient satisfaction were evaluated. Positive margins were defined as any type of disease present 1 mm or less from any specimen edge. RESULTS: Positive margin status did not differ between the 2 groups (28% vs. 31%). The volume of tissue removed was significantly less in the CAL group (49 vs. 66 mL, P = .002). Re-excisions were similar in both groups. CAL was superior in ease of lumpectomy, quality of specimen, acute surgical cosmesis, short-term cosmesis, patient satisfaction, and overall procedure time for the patient. CAL had a lower invasive positive margin rate (11% vs. 20%, P = .039) but a higher observed ductal carcinoma in situ-positive margin rate (30% vs. 18%, approaching statistical significance, P = .052). CONCLUSIONS: CAL is a preferred alternative to standard wire localization because it provides a palpable template, removes less tissue and improves cosmesis, decreases overall procedure time, and is more convenient for the patient and surgeon.

Cosmetic outcome and incidence of infection with the MammoSite breast brachytherapy applicator.

We present our results regarding the cosmetic outcome achieved and the rate of infection using the MammoSite breast brachytherapy applicator to treat patients with partial breast irradiation. In addition, factors associated with cosmetic outcome and infection are analyzed. The study population consisted of 30 patients with early stage breast cancer treated using the MammoSite device from October 28, 2002, to February 13, 2004. Cosmetic outcome was analyzed for its association with the following parameters: volume of the balloon, balloon-to-skin distance, maximal skin point dose per fraction, V100 (percent of volume that received 100% of the prescription dose), V150 (percent of volume that received 150% of the prescription dose), and V200 (percent of volume that received 200% of the prescription dose). The occurrence of infection at the time of treatment and during follow-up was also recorded. At a median follow-up of 13 months (range 1-16 months), 53.3% of the patients (16/30) were reported to have an excellent cosmetic outcome and 40.0% (12/30) had a good cosmetic outcome. Excellent cosmetic outcome was associated with a greater mean balloon-to-skin distance compared to those who achieved a good cosmetic outcome (1.5 cm versus 1.2 cm) (p = 0.164). The mean V100, V150, and V200 of those in the excellent cosmetic outcome group were 92.1%, 34.5%, and 7.6% versus 93.0%, 34.7%, and 7.6% in the good cosmetic outcome group (p = 0.642, 0.926, and 0.853), The mean balloon volumes were 47.7 cm3 and 56.9 cm3, respectively (p = 0.063) in the excellent and good outcome groups. The mean maximal skin doses per fraction in the excellent and good outcome groups were 354.8 cGy and 422.3 cGy (p = 0.286), respectively. Infection occurred in 13.3% of the patients (4/30). An excellent or good cosmetic outcome was achieved in 93.3% of patients and infection occurred in 13.3% of patients treated with the MammoSite breast brachytherapy applicator. Excellent cosmetic outcome was associated with a greater balloon-to-skin distance, lower maximal skin dose per fraction, and smaller mean balloon volume; however, the results did not reach statistical significance.

Office-based cryoablation of breast fibroadenomas with long-term follow-up.

Approximately 10% of women will experience a breast fibroadenoma in their lifetime. Cryoablation is a new treatment that combines the better attributes of the current standards: surveillance and surgery. It is a minimally invasive office-based procedure that is administered without the use of general anesthesia, involving minimal patient discomfort and little to no scarring. This work aimed to establish the long-term (2-3 years) efficacy, safety, and satisfaction of the procedure, as well as the impact of cryoablation on mammogram and ultrasound images. Thirty-seven treated fibroadenomas were available for assessment with an average follow-up period of 2.6 years. Of the original 84% that were palpable prior to treatment, only 16% remained palpable to the patient as of this writing. Of those fibroadenomas that were initially < or = 2.0 cm in size, only 6% remained palpable. A median volume reduction of 99% was observed with ultrasound. Ninety-seven percent of patients and 100% of physicians were satisfied with the long-term treatment results. Mammograms and ultrasounds showed cryoablation produced no artifact that would adversely affect interpretation. Cryoablation for breast fibroadenomas has previously been reported as safe and effective both acutely and at the 1-year follow-up mark, and thus has been implemented as a treatment option. At long-term follow-up, cryoablation as a primary therapy for breast fibroadenomas demonstrates progressive resolution of the treated area, durable safety, and excellent patient and physician satisfaction. The treatment is performed in an office setting rather than an operating room, resulting in a cost-effective and patient-friendly procedure. Cryoablation should be considered a preferred option for those patients desiring definitive therapy for their fibroadenomas without surgical intervention.

Surface optimization technique for MammoSite breast brachytherapy applicator.

PURPOSE: We present a technique to optimize the dwell times and positions of a high-dose-rate (192)Ir source using the MammoSite breast brachytherapy applicator. The surface optimization method used multiple dwell positions and optimization points to conform the 100% isodose line to the surface of the planning target volume (PTV). METHODS AND MATERIALS: The study population consisted of 20 patients treated using the MammoSite device between October 2002 and February 2004. Treatment was delivered in 10 fractions of 3.4 Gy/fraction, twice daily, with a minimum of 6 h between fractions. The treatment of each patient was planned using three optimization techniques. The dosimetric characteristics of the single-point, six-point, and surface optimization techniques were compared. RESULTS: The surface optimization technique increased the PTV coverage compared with the single- and six-point methods (mean percentage of PTV receiving 100% of the prescription dose was 94%, 85%, and 91%, respectively). The surface method, single-point, and six-point method had a mean dose homogeneity index of 0.62, 0.68, and 0.63 and a mean full width at half maximum value of 189, 190, and 192 cGy/fraction, respectively. CONCLUSION: The surface technique provided greater coverage of the PTV than did the single- and six-point methods. Using the FWHM method, the surface, single-, and six-point techniques resulted in equivalent dose homogeneity.

Ductal lavage in the high-risk patient.

BACKGROUND: [corrected] This analysis was conducted in a single-surgeon clinical practice to evaluate the utility and practicality of performing ductal lavage in a population determined to be at high risk for breast cancer. METHODS: One hundred twenty patients with negative mammograms and/or negative breast examinations had nipple aspiration and ductal lavage performed by a single surgeon. All were at high risk either according to Gail risk score, a previous breast carcinoma, or nipple discharge. RESULTS: One hundred twenty patients underwent nipple aspiration. Thirty-two did not undergo lavage: 29 had no fluid, and 3 had unsuccessful cannulation. Eighty-eight underwent lavage: 15 had insufficient epithelial content, 51 had benign cytology, and 22 had abnormal cells. Of the 22, 20 had mild atypia, 1 had marked atypia, and 1 had malignant cells. CONCLUSIONS: Ductal lavage can be done in a surgical practice and can stratify risk for the individual patient. This is important to both patient and surgeon in formulating a treatment plan based on objective cytologic criteria.

Ductal lavage using medically aseptic technique in women at high risk for breast cancer.

Ductal lavage of the breast is a minimally invasive procedure used to collect epithelial cells from the lumen of the ductolobular system for cytologic analysis. The purpose of this study was to determine the safety of using an aseptic technique in performing ductal lavage. The study included 114 consecutive patients at high risk for breast cancer with clinically negative mammograms and no palpable masses. Ductal lavage could not be performed on 32 of the 114 patients (28%): 26 because nipple aspirate fluid could not be obtained, and 6 because a fluid-yielding duct could not be cannulated. Ductal lavage was successfully performed on 82 patients (72%). Local anesthetic cream was used on the nipple area and local anesthetic was infused into each duct. The nipple, the cup of the nipple aspirator device, and any dilator tools were cleansed with alcohol before use. Separate sterile microcatheters were used for each duct. Sterile saline solution was used for the infusions. No patient reported any symptoms indicating infection after lavage. Cytologic analysis from the 82 lavage cases showed 45 benign cells (55%), 17 cases of mild atypia (21%), 1 case of marked atypia, and 1 case with malignant cells. Eighteen samples (22%) had inadequate cellularity for medical diagnosis. The results of the study indicate that an aseptic technique is safe and appropriate for ductal lavage of the breast.

Cryoablation treatment of benign breast lesions with 12-month follow-up.

OBJECTIVE: Eighty percent of all breast biopsies reveal benign findings. The most common benign tumor is a fibroadenoma. Despite their benign nature, many women eventually choose to have their bothersome lumps surgically removed. We report the use of cryoablation to treat these benign breast lesions with minimum 12-month follow-up. METHODS: After receiving Institutional Review Board approval, a prospective nonrandomized trial was initiated in June 2000. Ultrasound-guided cryoablation of core biopsy-proven benign fibroadenomas, other benign breast nodules, or nodular fibrocystic change was performed on 78 lesions in 63 patients. Eighty-five percent of lesions treated were benign fibroadenomas. The cryoablation procedure consisted of a double freeze-thaw cycle that lasted between 6 and 30 minutes and was performed most often in an office setting. Each patient was serially evaluated for treatment efficacy, complications, and patient satisfaction. RESULTS: Sixty-four of 78 lesions (mean size 2.0 cm [range 0.8 to 4.2]) were followed-up for at least 12 months after cryoablation per protocol, which included 53 fibroadenomas. At 1 year, ultrasound tumor volume resorption was 88.3% overall (87.3% for fibroadenomas), and 73% of the entire group became nonpalpable to both clinician and patient (75% for fibroadenomas). Two of the fibroadenoma patients had their palpable residual nodule excised, both revealing necrotic debris and no viable tumor in the treated volume. Serial mammograms showed resorption of the lesion leaving minimal residual density without calcifications. Cosmesis was excellent with only a small scar remaining at the probe insertion site. There was no report of visual or palpable volumetric deficit. Patient satisfaction was good to excellent in 92% of cases. CONCLUSIONS: Cryoablation was successful in treating core biopsy-proven benign breast lesions in 63 patients. At 12 months, we found gradual resorption of treated tissue with no cosmetic deficit. Ultrasound-guided cryoablation is an effective and safe treatment for benign breast lesions, as seen at 12-month follow-up, and offers an office-based, minimally invasive alternative to surgical excision.

Office-based breast ductoscopy for diagnosis.

OBJECTIVE: Ductoscopy is an evolving technology that has been used primarily and historically in conjunction with open surgical procedures. New technical improvements allow intraductal biopsy and therefore its application in the clinical setting for diagnostic evaluations of the breast. This study looks at the initial use of intraductal biopsy in a variety of settings from an academic university practice to a private single-surgeon office. METHODS: This is a multicenter retrospective series of 88 patients undergoing ductoscopy of > or =1 duct for the diagnostic workup of common breast problems. The procedures were done with the patient under local anesthesia, and intraductal biopsy specimens were taken and analyzed as breast cytology samples. RESULTS: Of the 88 patients undergoing office ductoscopy, nipple discharge was the most common indication (n = 83 patients; 94% to 66% spontaneous and 34% elicited). Fifty-five percent were high risk for breast cancer by history. The majority of patients had normal previous mammograms: 48 Breast Imaging-Reporting and Data System (BIRADS) 1, 24 BIRADS 2, and 7 BIRADS 3 to 5. The most common finding was papilloma present in 29 (32%) patients by endoscopy. Only 31% of patients had a history of brown or bloody nipple discharge. A wide variety of other endoscopic abnormalities were seen and biopsied. The average number of biopsies per patient was 2 with 18 (20.5%) having severe or malignant atypia. Further follow-up and management of these more concerning abnormalities is currently ongoing. CONCLUSIONS: These results indicate that office ductoscopy with biopsy is both feasible and does identify suspicious or malignant atypia in patients with expressed or spontaneous nipple fluid.

Office-based cryoablation of breast fibroadenomas: 12-month followup.

BACKGROUND: Fibroadenomas comprise between 30% and 50% of all breast biopsies. Despite their benign nature, many women have their fibroadenomas surgically removed. We previously reported on a minimally invasive therapy using cryoablation to treat fibroadenomas. We now report on 12-month followup using this technique. STUDY DESIGN: A prospective, nonrandomized trial was initiated in June 2000 with IRB approval. The Visica Treatment System was used to cryoablate 70 biopsy-proved fibroadenomas in 57 patients using a freeze-thaw-freeze cycle lasting 6 to 30 minutes. Each patient was serially evaluated for safety, efficacy, and satisfaction. RESULTS: Fifty-seven fibroadenomas (mean 2.1 cm, range 0.8 to 4.2 cm) in 47 patients were followed for 12 months. At 1 year, with 89% median tumor volume reduction measured by ultrasonography, 75% of fibroadenomas were nonpalpable. There were no adverse events and only minor complications. Two patients (4%) had their lesions excised after 12 months; pathology revealed no viable fibroadenoma. Serial mammograms showed resorption of the fibroadenoma leaving minimal residual density without calcifications. Cosmesis was excellent with no volume deficit, as no tissue is removed. Ninety-one percent of patients were satisfied at 12 months. CONCLUSIONS: Cryoablation is safe and effective in treating breast fibroadenomas. It offers a nonsurgical, office-based treatment that is well tolerated by patients and accurately monitored with ultrasonographic guidance. At 12 months we found progressive tumor volume reduction and reduced palpability, with no volume deficit, excellent cosmesis, and satisfied patients. Ultrasonography-guided cryoablation is a preferred option for treatment of breast fibroadenomas without open surgery.

Treatment volume and dose optimization of MammoSite breast brachytherapy applicator.

PURPOSE: Limited information has been reported on the dosimetry achieved with the MammoSite breast brachytherapy applicator. We present our results regarding the volume of treatment and a comparison of a single prescription point, single dwell position optimization technique with a six prescription point, multiple dwell position method. METHODS AND MATERIALS: Between October 14, 2002 and February 28, 2003, 21 patients with early-stage breast cancer were treated using the MammoSite device. The treatment was delivered in 10 fractions of 3.4 Gy/fraction, b.i.d., with a minimum of 6 hours between the daily fractions. CT of the lumpectomy cavity was obtained both with and without the inflated balloon. A planning target volume was constructed using a three-dimensional planning system. A three-dimensional expansion of the balloon surface was performed using the chest wall and skin as limiting structures. The volume of the inflated balloon was removed from this volume, and the volume of tissue treated in each patient was determined. A sequential expansion in 1-mm increments around the empty lumpectomy cavity was performed until the closest equivalent volume to the planning target volume was obtained. The treatment for the patients in this study was planned using both a single prescription point, single dwell position optimization technique and a six-prescription point, multiple dwell position technique. The single prescription point method has been described in a previous publication. The six-prescription point method used six points placed 1 cm from the balloon surface. Four points are in a plane transverse to the balloon axis perpendicular to the axis of the catheter, and two points are placed along the axis of the catheter. The prescription points along the catheter axis are used to compensate for the decreased dose coverage owing to anisotropy dose distribution of the source. The Nucletron HDR Plato Brachytherapy planning system was used to optimize the source positions and dwell times. RESULTS: The volume of breast tissue treated by the MammoSite device was equal to the volume encompassed by a mean 1.6-cm (SD, 0.1) margin around the empty lumpectomy cavity. Compared with the single prescription point optimization method, the six prescription point method provided better dose coverage, with a mean percentage of volume receiving 90% of the prescription dose of 97.2% (SD = 2.1) vs. 89.5% (SD = 4.6) for the single-point method. The mean percentage of volume receiving 100% of the prescription dose was 88.9% (SD = 3.3) for the six-point method vs. 77.6% (SD = 6.1) for the single-point method. However, compared with the single-point method, the six-point optimization method resulted in treatment that was less uniform, with a mean dose homogeneity index of 0.62 (SD =.07) vs. 0.66 (SD =.08) for the single-point method. CONCLUSION: The volume of normal breast tissue treated by the MammoSite device is comparable to other methods of interstitial brachytherapy that treat a 1-2-cm margin of tissue around the excision cavity. The six-prescription point, multiple dwell position method improved dose coverage with a slight decrease in dose homogeneity. The six-point method offers greater reliability of dose coverage compared with the single-point method by providing an increased number of reference points.

Current comprehensive assessment and management of women at increased risk for breast cancer.

The potential for reducing the risk of breast cancer through selective estrogen receptor modulators, aromatase inhibitors, and surgery has generated interest in the use of quantitative models of risk assessment. With the addition of ductal lavage cytology to traditional epidemiologic risk factors, a discovery of cellular atypia can result in refinement of assigned risk values, while simultaneously optimizing patient selection for selective estrogen receptor modulators utilization. In view of increasing complexity in this arena, a Risk Assessment Working Group was formed to outline management strategies for the patient at an elevated risk for the development of breast cancer. No longer a statistical exercise, quantitative risk assessment is part of basic breast care and comprehensive management includes a discussion of the following: ductal lavage for improved risk stratification, multiple options for risk reduction, and high risk surveillance strategies that might incorporate investigational imaging protocols.

Assessment of Her-2/Neu status by immunohistochemistry and fluorescence in situ hybridization in mammary Paget disease and underlying carcinoma.

HER-2/Neu overexpression is seen in 20% to 30% of invasive breast carcinomas and has been reported in as many as 80% of high-grade infiltrating carcinomas. Earlier studies have suggested that 100% of the tumor cells in mammary Paget disease show overexpression of HER-2 protein. We undertook this study to assess HER-2 status of mammary Paget disease and of the underlying breast carcinoma, when present, by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Formalin-fixed, paraffin-embedded tissue from 20 cases of mammary Paget disease were analyzed for HER-2 status by IHC and FISH. IHC for estrogen receptor (ER) was also performed. The patients ranged in age from 34 to 88 years, with a mean age of 62 years. Eighty percent of the cases showed strong overexpression (3+) of HER-2 protein by IHC, and all of these cases showed more than 5-fold amplification of the HER-2 gene by FISH. The remaining 4 cases, which were negative for HER-2/Neu by IHC, showed no amplification by FISH. All of the latter cases expressed ER, whereas no case that overexpressed HER-2 expressed ER. Sixteen cases had an underlying tumor, which was in situ in 6 cases. The underlying tumors were identical to the Paget disease with respect to their HER-2/Neu overexpression by both IHC and FISH. HER-2 overexpression was identified in 80% of our cases of Paget disease. There was 100% concordance between HER-2 protein overexpression by immunohistochemistry and gene amplification in both the Paget and the underlying tumor. Moreover, all of the cases negative for HER-2 overexpression expressed ER, whereas those positive for HER-2 did not.

Office-based ultrasound-guided cryoablation of breast fibroadenomas.

BACKGROUND: Fibroadenomas commonly found by palpation and routine mammography account for approximately 20% of open surgical breast biopsies. Alternatives to open surgery include tumor removal using an automated coring device and tumor ablation using heating or cooling elements. We report our initial experience with cryoablation of biopsy-proven benign fibroadenomas. METHODS: A table-top cryoablation system employing a 2.4-mm cryoprobe was used to treat biopsy-proven benign fibroadenomas up to 4 cm in maximum diameter in a prospective nonrandomized fashion. The cryoprobe was placed under ultrasound guidance. Using a treatment algorithm based on fibroadenoma size, all tumors were subjected to two freeze cycles with an interposing thaw. Skin appearance and temperature, probe temperature, iceball size, and patient comfort were closely monitored during the procedure. Follow-up examinations including ultrasonography and photographs were scheduled for up to 12 months postablation. RESULTS: Fifty patients with 57 core biopsy-proven benign fibroadenomas were treated. Seven early cases were treated in an ambulatory surgery center setting. The remaining procedures were completely office-based using only local anesthetic. Tumor diameter varied from 7 mm to 42 mm (mean 21 mm). The iceball engulfed the target lesion in each case. Transient postoperative side effects were local swelling and ecchymosis. Postoperative discomfort rarely required medication beyond acetaminophen or ibuprofen. Lesions showed progressive shrinkage and disappearance over 3 to 12 months. No skin injury was noted and appearance remained excellent. Patient satisfaction was excellent. CONCLUSIONS: With office-based use of ultrasound-guided cryoablation for fibroadenomas there was little or no pain, target lesions were reduced in size or eliminated, scarring was minimal, cosmesis outstanding, and patient satisfaction was excellent. Cryoablation offers a useful office-based alternative to surgical excision of benign fibroadenomas.