bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P4-14-05: Skin sparing mastectomy – thorough breast tissue removal leads to a low local recurrence rate of breast cancer
Authors: Paily AJ , Drabble EH
Published: August 2014

Introduction: Skin sparing mastectomy (SSM) has the dual advantage of being an acceptable treatment for breast cancer as well as preserving a skin envelope for better aesthesis and cosmesis. However, SSM and immediate breast reconstruction for early breast cancer is not based on level-1 evidence. Even though oncological recurrence is equivalent to that with skin removing mastectomies, most studies have only short term follow-ups. Local Recurrence (LR) or the threat of it is becoming an increasing issue for us as 1 in 4 will succumb from local recurrence. We present local recurrence (LR) and systemic recurrence (SR) rates and the aesthetic results following SSM with or without immediate reconstruction.

Methods and materials: Over a period of 10 years, 249 patients undergoing SSM with or without immediate reconstruction were identified from a prospectively recorded database and complete details of all their treatments and outcomes were assessed. The reconstructive methods employed included Transverse Rectus Abdominus Myocutaneous (TRAM) flap, Latissimus Dorsi (LD) flap in isolation or along with an implant and subpectoral implant insertion. LR and SR rates were determined. Pathological examination of biopsies from the skin flaps after SSM, were also analysed.

Results: Of the 249 patients who underwent SSM, only 34 did not have immediate breast reconstruction. The overall LR and SR rates were 0.4% and 4.4% respectively. 76 patients underwent SSM and TRAM flap reconstruction (1 LR and 5 SR). 33 patients had LD flap reconstruction (no LR and 1 SR). 61 patients were given LD flap reconstruction with implants (no LR and 4 SR). SSM and insertion of sub-pectoral implants was performed on 45 patients (no LR and no SR). 34 patients underwent SSM without immediate reconstruction (no LR, 1 SR). All 249 patients had no evidence of residual breast tissue in subcutaneous flap biopsies. Of the 215 patients who underwent immediate reconstruction, 140 had a good aesthetic result (65%). Individually, TRAM flap and LD flap with implant insertion each produced the best aesthetic result (74%). While reconstructions with LD flaps alone did result in a good aesthetic result in 70% of patients, it also had the poorest aesthetic result (12%) compared to the other three groups.

Conclusion: SSM with or without immediate breast reconstruction performed in our unit has shown a very low rate of LR compared to that in literature. In addition, flap biopsies have shown no residual breast tissue in our patients highlighting that thorough removal of breast tissue at skin sparing mastectomy leads to low LR rates. Our systemic recurrence rates are much higher than local recurrence rates, but are still as expected or slightly lower than expected. Our approach therefore achieves thorough removal of breast tissue and we believe that this leads to a low local recurrence rate, but with good aesthetic results.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-05.
Abstract P4-14-06: Contralateral Prophylactic Mastectomy and Survival: Selection Bias or True Survival Benefit?
Authors: Yao Katharine , Du Hongyan , Tomasz Czechura , Winchester David P , Winchester David J , Hou Ningi , Huo Dezheng
Published: August 2014

Withdrawn by Author

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-06.
Abstract P4-14-08: Intraoperative ultrasound guidance for excision of non-palpable breast cancer
Authors: Barentsz MW , van Dalen T , Gobardhan PD , Bongers V , Perre CI , Pijnappel RM , van den Bosch MA , Verkooijen HM
Published: August 2014

Background: The effectiveness of intraoperative ultrasound (IOUS) for preoperative localization of non-palpable breast cancers within the operation theatre has not been studied extensively. In this prospective cohort study, we compared margin status, re-excision rate and excised volume of IOUS to guidewire localization (GWL).

Methods: A total of 258 consecutive patients with non-palpable invasive breast cancer underwent breast conserving surgery between 1999–2010. GWL was performed in 138 (54%) and IOUS in 120 (46%) patients. Tumour dimensions, resection volume, margin status and re-excision rates were compared by means of multivariate regression analysis. Calculated resection ratios, i.e. indicating the amount of excess tissue resection, were calculated by dividing the total resection volume by the optimal resection volume (the tumor diameter plus a 1.0 cm margin) and compared between the groups.

Results: The groups were similar in terms of age, histological subtype and presence of DCIS. Lesions in the IOUS group were larger (1.24 vs. 0.98 cm), while lesions in the GWL group consisted more often of microcalcifications only (19% vs. 3%). Tumour free resection margins were obtained in more than 93% of patients (93.5% with GWL vs. 93.3% with IOUS, P = .958) and re-excision was performed in 11.0% of patients undergoing GWL and 12.5% of patients undergoing IOUS (P = .684). In both groups, resection volumes were similar, but IOUS led to more optimal tissue resection (calculated resection ratio 4.33 vs 3.30, P = .018). After adjustment for tumor diameter, radiological findings and presence of DCIS, the difference in calculated resection volumes was no longer significant.

Conclusion: For localization of non-palpable breast cancer, IOUS is a reliable alternative to GWL, as it achieves similar results in terms of complete tumour removal, re-excision rate and excised volume.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-08.
Abstract P4-14-10: Atypical Ductal Hyperplasia diagnosed on directional vacuum-assisted biopsy: is surgical excision mandatory?
Authors: Chauvet M-P , Rivaux G , Farre I , Houpeau J-L , Giard S , Ceugnart L
Published: August 2014

Background: The incidence of atypical ductal hyperplasia (ADH) is increasing due to mass screening. Because of the underestimation risk of malignancy, the management remains controversial. Our goal was to analyze clinicopathologic features of patients with ADH diagnosed on directional vacuum-assisted biopsy (DVAB). The objectives of this continuous retrospective study were to evaluate the underestimation rate of malignancy and to identify predictors of upgrade to carcinoma.

Methods: Between 2003 and 2010, 3159 patients underwent stereotactic DVAB in our institute. We retrospectively evaluate clinical, mammographic and pathological features of 298 cases of ADH who underwent surgical excision in our center (93.1%). Patients with concurrent history of breast cancer, intraductal carcinoma (DCIS) associated, or with no follow-up or surgical excision on place were excluded. Histological scar of macrobiopsy was systematically searched in surgical specimens. A pathologic upgrade was defined by presence of invasive cancer or DCIS on surgical specimen. Statistical tests used were the chi-square or Fisher's exact test.

Results: Among the 298 studied DVAB, 224 ADH were isolated (75.2%), 46 associated to flat epithelial atypia (15.4%) and 28 to lobular neoplasia (9.4%). 98.4% patients presented microcalcifications at diagnosis. In 52 cases, lesions were upgraded to DCIS (n = 38) or invasive cancer (n = 14). The underestimated rate was 17.5%. In 67.3% cases, upgrade lesions were low or intermediate grade DCIS. Only the history of contralateral breast cancer was significantly correlated with the underestimated rate (p = 0.04). There was no statistical difference between these 52 cases and the 246 others for: family history, size of calcification, sampling number, histological lesion, and quality of calcifications removal.

Conclusions: In this study, DVAB may not be considered a therapeutic procedure in case of ADH, even in the case of complete removal of microcalcifications. It is still challenging to identify a subgroup of ADH cases with a low upgrade rate.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-10.
Abstract P4-15-02: Timing of infectious complications following breast conserving therapy with catheter-based accelerated partial breast irradiation
Authors: Haynes AB , Bloom ES , Bedrosian I , Kuerer HM , Hwang RF , Caudle AS , Hunt KK , Graviss L , Chemaly RF , Tereffe W , Shaitelman SF , Babiera GV
Published: August 2014

Background: Accelerated partial breast irradiation (APBI) has been introduced as an alternative to whole breast irradiation as part of breast conserving therapy for selected patients. The long-term outcomes remain under investigation. Previous publications have emphasized early postoperative infections with APBI with less focus on delayed infection. In the current study, we evaluated patients enrolled on a prospective registry trial for infectious complications after treatment with catheter-based APBI.

Methods: Patients who underwent single-entry catheter-based APBI were identified from a single-institution prospective registry from 2009 to 2011. Data regarding treatment, patient comorbidities, complications, and outcomes were obtained from registry and retrospective chart review. Infectious complications were assessed from the date of APBI catheter insertion and were classified as early (≤30 days) or delayed (>30 days). All patients were maintained on oral antibiotics while the catheter was in place.

Results: A total of 91 patients with 92 cases of primary breast cancer were enrolled on a prospective registry at a comprehensive cancer center between 2009 and 2011 and treated with single-entry catheter-based APBI. The median follow-up time was 76.2 weeks. A temporary catheter was placed at the time of initial operation in 40 cases (43.5%) and left in place a median of 6 days prior to definitive catheter insertion. There were 20 patients (21.7%) who required re-excision. Overall, breast infection occurred in 13 (14.1%) patients. Three (3.3%) patients had infection within 30 days of catheter placement and 10 (10.9%) occurred more than 30 days after catheter insertion (median 112.5 days, interquartile range 51–154). Eight patients were managed with oral antibiotics alone on an outpatient basis. The remainder required a combination of admission, intravenous antibiotics, and aspiration of abscess. One patient underwent operative drainage.

Conclusion: We found an overall infection rate of 14.1% in patients treated with catheter-based APBI. This is consistent with other reports; however, we found that the majority of infections occurred more than 30 days after definitive catheter placement. Vigilance for infectious complications must continue beyond the immediate treatment period in patients undergoing catheter-based APBI. Most infections following APBI can be managed on an outpatient basis without operative intervention.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-15-02.
Abstract P4-15-05: Long-term outcome of breast cancer patients treated with radiofrequency ablation
Authors: Earashi M , Noguchi M , Motoyoshi A , Komiya H , Fujii H
Published: August 2014

Background: Radiofrequency ablation (RFA) is considered to be the most promising non-surgical ablation technique for the treatment of small breast cancer. In feasibility studies, the ablated tumor was surgically removed after RFA, and the tumor cell viability were assessed by histological and/or immunohistological examinations. However, these assessments of tumor viability do not take the place of long-term follow-up in patients treated with RFA alone, because they do not allow for them to be followed up for recurrence after RFA, or to determine if there were any undesirable complications of this procedure. At present, few data are available regarding long-term follow-up of patients treated with this modality.

Methods: Since 2005, we have performed RFA and sentinel lymph node (SLN) biopsy in 19 cases with invasive breast cancer less than 2.0 cm in greatest diameter. After SLN biopsy, a primary electrode (seven-array model 70 Starburst needle electrode; RITA Medical Systems, Mountain View, CA) was inserted into the tumor under real-time US guidance. Then, the prongs of the needle electrode were deployed over a distance of 3 cm in all cases, and the RF generator (RITA model 1500) was activated and set to automatic, with power at 20 W, temperature of 95°C, and an ablation time of 15 min. Axillary lymph node dissection (ALND) was performed in patients with positive SLNs. Several months after RFA therapy, the ablated tumor tissue was excised by multiple mammotome biopsy and examined histologically or immunohistochemically with H&E staining, nicotinamide adenine dinucleotide (NADH)-diaphorase staining, and single-stranded (ss) DNA staining. All cases were followed-up after breast radiation and systemic therapies.

Results: The mean tumor size based on the ultrasonographic maximum dimension was 1.3 cm (range: 0.5–2.0 cm). Although complete response was histologically confirmed in only 8 cases, NADH-diaphorase and ssDNA staining did not demonstrate any viable tumor cells in any of the ablated lesions. At a mean follow-up of 60 months (follow-up range, 37–82 months), there were no cases of in-breast recurrence, although one patient died due to hepatic metastases. Cosmesis of the conserved breast was excellent or good in all of the cases, but a hard lump was persistent after RFA in half of the cases.

Conclusions: The long-term outcome of patients treated with RFA is encouraging with regard to cosmesis and local control. However, a persisted lump can cause patient discomfort, anxiety and fear. Therefore, further studies are needed to establish the optimal technique. Moreover, a prospective study will be required to determine the equivalency in local recurrence rates between the RFA therapy and conventional breast-conserving treatment.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-15-05.
Abstract P4-16-02: A survival benefit from locoregional radiotherapy for node-positive and CMF treated breast cancer is most significant in Luminal A tumors
Authors: Voduc D , Cheang MCU , Tyldesley S , Chia S , Gelmon K , Speers C , Nielsen TO
Published: August 2014

Background: Between 1978–1986, 318 premenopausal women treated with mastectomy for lymph node positive breast cancer, were randomized to CMF chemotherapy alone vs. CMF chemotherapy and adjuvant radiotherapy (RT) to the chest wall and regional lymph nodes. After 15 years of follow-up, post-mastectomy RT was associated with a statistically significant 29% relative risk reduction in mortality. Recent evidence suggests that Luminal A tumors, identified using hormone receptors and Ki67, have a particularly favorable prognosis. We retrospectively identified the Luminal A tumors from this clinical trial cohort to determine if the response to postmastectomy RT differed among Luminal A and non-Luminal A tumors.

Methods: 203 archival breast tumor samples from this study were used to construct a tissue microarray. Luminal A tumors were identified using an immunopanel consisting of: estrogen receptor, progestorone receptor, Her2, and Ki67. Luminal A tumors were defined as either ER or PR positive, Her2 negative, and Ki67 < 14%. Kaplan-Meier estimates and the log-rank test were used to test the differences in locoregional relapse free survival (LRFS) and breast cancer specific survival (BCSS). Interaction between treatment and Luminal A/Non-luminal A were tested using Cox regression analysis.

Results: The intrinsic subtype was successfully determined in 144 breast tumors, and 49 were classified as Luminal A (34%). Survival outcomes at 10 years are summarized in Table 1:

Conclusion: Our study examines the outcome of Luminal A tumors in patients with higher risk (premenopausal and lymph node positive) breast cancer treated with CMF chemotherapy. We observed that both subjects with Luminal A tumors and non-Luminal A tumors appear to demonstrate improved locoregional control with post-mastectomy RT, although this was only significant for Luminal A tumors. The non-significant interaction test suggests that there is no observable difference in radiosensitivity in this limited study population. However, the improvement in BCSS with post-mastectomy RT was only significant in the subjects with Luminal A tumors, and the interaction test was statistically significant.

Our results raise the possibility that patients with non-Luminal A breast tumors are at higher risk of occult metastatic disease at presentation, and may not derive a survival benefit with improved locoregional control in the setting of CMF chemotherapy. In contrast, locoregional control has a significant effect on survival with Luminal A tumors. Our study suggests that a favorable Luminal A diagnosis should not be a reason to omit regional radiotherapy in node positive patients, as it is this subgroup that may derive the greatest benefit.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-16-02.
Abstract P4-16-04: Outcome of stage II/III breast cancer treated with neoadjuvant versus adjuvant radiotherapy in British Columbia.
Authors: Lohmann AE , Voduc D , Speers C , Chia S
Published: August 2014

Backgroud: Neoadjuvant radiotherapy (NRT) is generally recommended after systemic therapy for inoperable stage III breast cancer. At the BCCA, neoadjuvant radiation is also frequently offered for patients with operable node positive disease after neoadjuvant chemotherapy. There is a lack of randomised trial data comparing outcomes in stage II/III breast cancer when radiation therapy is delivered neoadjuvantly versus adjuvantly.

Aim: The primary objective of this study is to assess the clinical outcomes, as measured by relapse-free survival (RFS), overall survival (OS), and breast cancer-specific survival (BCSS), of women with stage II/III breast cancer treated with neoadjuvant chemotherapy and either neoadjuvant or adjuvant radiotherapy.

Methods: Patients were identified by linking the Breast Cancer Outcomes Unit (BCOU) with the British Columbia Cancer Agency Pharmacy data repository. Inclusion criteria included: Female, referred to BCCA with newly diagnosed disease, clinical stage II or III breast cancer, neoadjuvant chemotherapy, breast surgery performed as part of the initial treatment plan, RT (given adjuvantly or neo-adjuvantly to the breast/chest wall +/− regional nodes). Patients were excluded if they had a previous or synchronous in situ or invasive breast cancer. Demographic data, treatment characteristics, ER, PR and HER-2 status (when available) were extracted. Data was analyzed using descriptive statistics and Kaplan Méier curves survival analyses were produced using SPSS, V. 14.

Results: Between Jan 1, 1995 and Dec 31, 2008, 687 patients with stage II/III disease were identified. 394 patients received neo-adjuvant and 293 patients received adjuvant radiation. Patients treated with neoadjuvant vs. adjuvant RT differed in age (median: 51yrs vs. 49yrs, p < 0.001), margin status (86.5% negative/5.1% positive/ 8.4% unknown vs. 94.2% negative/1.7% positive/4.1% unknown, p = 0.02), surgery (94.2% vs. 87.7% mastectomy, p = 0.003), and type of chemotherapy (50.3% vs. 24.6% anthracycline only, p < 0.001) respectively. No differences in 5-year RFS (60.0 vs. 64.8 %, respectively, p = 0.07), 5 year BCSS (67.9 vs. 73.1 %, respectively p = 0.17) and 5-year OS (66.2 vs. 72.5 %, respectively, p = 0.06) were seen in the neoadjuvant vs. adjuvant population.

Conclusion: Within the limitations of this retrospective study, the sequence of use of radiation pre-operative compared to post-operative following neoadjuvant chemotherapy appears to have similar clinical outcomes.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-16-04.
Abstract P4-16-06: Radiotherapy to the Primary Tumor Is Associated with Improved Survival in Stage IV Breast Cancer
Authors: Morgan SC , Caudrelier J-M , Clemons MJ
Published: August 2014

Background: In patients found to have metastatic disease at the time of breast cancer diagnosis, the role of local therapy is undefined. Numerous retrospective analyses have suggested that surgery and/or external beam radiotherapy (EBRT) directed at the primary tumor may improve overall survival (OS). All these analyses, however, are subject to significant selection bias. The current retrospective analysis of a large registry dataset attempts to limit the effect of this bias.

Methods: The study population consisted of women in the Surveillance, Epidemiology, and End Results (SEER) program database diagnosed with stage IV breast cancer between 1988 and 2009. Only those patients for whom surgery to the primary tumor was recommended but was not undertaken (due to patient refusal or other uncategorized reasons) were included. In this population of patients deemed candidates for surgery, the association between receipt of primary tumor-directed EBRT and overall survival was studied. Descriptive statistics were used to characterize the study population. OS was estimated using the Kaplan-Meier (KM) method. Univariate and multivariate Cox regression were used to identify factors associated with OS.

Results: A total of 3,529 cases were analyzed. EBRT was received in 768 cases. Median age at diagnosis was 68 years (IQR, 56–79 years). Median follow-up by reverse KM estimate was 98 months (range, 0–252 months). On univariate analysis, EBRT was associated with improved OS (hazard ratio 0.80, 95% CI 0.74–0.87, p < 0.001). 1-year, 3-year, and 5-year OS was 56.9%, 24.2%, and 10.7% respectively in those receiving EBRT and 44.3%, 16.6%, and 7.2% respectively in those not receiving EBRT. Median OS in those receiving EBRT was 15 months compared to 7 months in those not receiving EBRT. In a multivariate Cox model taking into account receipt of EBRT, age at diagnosis, year of diagnosis, ethnicity, number of primary cancers, estrogen and progesterone receptor status, histologic grade, and size of primary tumor, EBRT remained significantly associated with improved survival (hazard ratio 0.86, 95% CI 0.76–0.97, p = 0.011).

Conclusions: In a population of women presenting with metastatic breast cancer, all of whom were deemed candidates for surgery to the primary tumor but who did not undergo surgery, receipt of EBRT was associated with improved OS. The observed 8-month absolute difference in median OS is clinically significant. This analysis could not account for performance status, extent of metastatic disease, co-morbidities, use of systemic therapies, and other potentially confounding factors. Only randomized studies, such as the Eastern Cooperative Oncology Group E2108 trial currently underway, will be able to definitively assess the value of local therapy directed at the primary tumor in this setting.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-16-06.
Abstract P4-16-09: Dosimetric feasibility and acute toxicity in a prospective trial of ultra-short course accelerated partial breast irradiation (APBI) using a multi-lumen balloon brachytherapy device
Authors: Khan AJ , Vicini FA , Brown S , Haffty BG , Kearney T , Dale R , Arthur DW
Published: August 2014

Background: Shorter courses of APBI with novel fractionation schedules are being investigated; a large randomized trial from Europe has recently shown the safety and efficacy of a single-fraction adjuvant approach (with limited follow-up). We designed a prospective trial to identify and address the potential radiobiological and logistical limitations of single-fraction, intraoperative APBI.

Methods: We designed a single-arm, multi-institutional, prospective phase II trial that sequentially treats three cohorts of women (each n=30) with three progressively hypofractionated schedules. Eligible women were age ≥ 50 years with unifocal invasive or in situ tumors ≤ 3.0 cm, excised with negative margins, and with negative lymph nodes and positive hormone-receptors. Using a reference schedule of 60 Gy delivered in 2 Gy fractions, and assuming tumor parameters: a/b = 4 Gy; a = 0.27 Gy-1, and repopulation parameters of: Teff = 26 days; delay time = 0 days, the reference tumor BED is ∼ 86 Gy4. We began with a schedule of 4 fractions of 7 Gy delivered twice-daily using a Contura MLB multi-lumen device. We defined very conservative dosimetric criteria for acceptability: maximum skin and rib dose to not exceed 100% of prescription dose, and V150 and V200 to not exceed 40 cc and 10 cc, respectively. Subsequent schedules are 3 fractions of 8.25 Gy and 2 fractions of 10.25 Gy, both delivered over 2 days. The primary endpoint is to exclude a local failure rate exceeding 10% with the upper limit of a 95% confidence interval.

Results: A total of 30 patients have been enrolled at the 7 Gy × 4 fractions dose-level and followed for a minimum of 6 months. The median skin dose as a percent of prescription dose (PD) was 84% (40–100) and the median rib dose was 71% (16–119). 96% of the PTV_eval received a median of 95% of PD (range 85–103). The V150 (range 14–48cc) and V200 (range 0–29cc) criteria were met in all cases. One breast infection occurred and was treated; 2 cases of symptomatic fat necrosis and 2 cases of symptomatic seromas occurred. No acute toxicities greater than CTCAE grade 2 have been observed.

Conclusion: Short-course APBI is dosimetrically feasible using the Contura MLB and appears to be tolerable in terms of acute toxicities. Our approach is based on well-defined radiobiological parameters and allows for an abbreviated course of treatment that is guided by full pathological review and the ability to objectively achieve and validate acceptable dosimetric criteria in each case. We have opened enrollment to the next schedule of 8.25 Gy for three fractions.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-16-09.
Abstract P4-16-11: Impact of receptor status on prognosis among breast cancer patients with brain metastases treated with Cyberknife radiosurgery
Authors: Fasola CE , Gibbs IC , Soltys SG , Horst KC
Published: August 2014

Purpose: Stereotactic radiosurgery (SRS) is increasingly used in the management of brain metastases. Receptor status is an important prognostic factor among women with breast cancer. The aim of this study was to evaluate the effect of receptor status on clinical outcomes in breast cancer patients with brain metastases treated with SRS.

Materials and Methods: We performed a retrospective review of 102 primary breast cancer patients with brain metastases treated with Cyberknife radiosurgery at Stanford University Medical Center between 2004 and 2011. The clinical characteristics, pathologic features, treatment details and clinical outcomes were reviewed. Median follow-up time was 18 months from the date of treatment with Cyberknife radiosurgery. All analyses were performed using SAS software, version 9.3 (SAS Institute, Cary, NC).

Results: Patients with Her-2/neu positive receptor status treated with trastuzumab had a significantly improved median overall survival after treatment with stereotactic radiosurgery compared to patients with Her-2/neu negative receptor status (27 months vs 7 months, p = 0.002) or patients with Her-2/neu positive receptor status who did not receive trastuzumab (27 months vs 12 months, p = 0.04). In contrast, patients with estrogen receptor, progesterone receptor and Her-2/neu negative receptor status had significantly worse median overall survival after treatment with stereotactic radiosurgery compared to patients with at least one positive receptor (8 months vs 17 months, p = 0.02). On multivariable analysis, Her-2/neu status emerged as the only significant predictor of survival (p = 0.01).

Conclusions: Her-2/neu receptor status was found to be a significant prognostic factor influencing survival among breast cancer patients with brain metastases treated with SRS. Importantly, the addition of treatment with trastuzumab among Her-2 neu positive patients significantly improved clinical outcomes.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-16-11.
Abstract P4-17-05: Reconstructive breast surgery using an acellular dermal matrix: prospective outcomes of an observational, cohort study (POBRAD).
Authors: Westbroek David , Kothari Ash , Hamed Hisham , Agbaje Olorunsola , Douek Michael
Published: August 2014

Withdrawn by Author

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-17-05.
Abstract P4-17-06: The use of specialist nurse-led clinics in preparation for reconstructive breast surgery.
Authors: Affan AM , Ali RA , Morton-Gittens JA , Perry A , Harry A , O'Donoghue JM , Rampaul R
Published: August 2014

Objective: To assess the effectiveness of a specialist nurse in a breast oncoplastic clinic. This was done by comparing patient reported outcome measures (PROMS) following information given about breast reconstructive surgery by either a specialist nurse or consultant surgeon.

Design & Methods: From June 2011 to December 2011 a study specific questionnaire was administered to patients who were considering breast reconstruction at the St. James Breast Service in Trinidad. A modified questionnaire was used which employed a Likert scale in order to provide a measure of patient satisfaction with the preoperative information and preparation provided by either a specialist breast cancer nurse (Group 1) as compared to the consultant breast surgeon (Group 2). The scale graded satisfaction levels from one to five where one represented patient dissatisfaction while five indicated complete satisfaction. Data was collated and analyzed using SPSS 17 with the significance level set at p = 0.05.

Results: Seventy-five (75) patients were obtained for the study. Sixty-three (63) of these patients responded adequately to the questionnaire resulting in an eighty-five percent (85%) response rate. There was a 97% overall satisfaction (n = 61) with the preoperative information given whether administered by the specialist nurse or the consultant surgeon. Ninety-five percent (95%) (n = 60) of patients indicated that verbal information from the consultant was extremely useful while eighty-seven percent (87%) (n = 55) of patients responded favorably to the information departed by the specialist nurse (X21.21; p = 0.271). Additonally, ninety-five percent (95%) (n = 60) were completely satisfied with the response from the consultant while ninety percent (90%) (n = 56) with that of the specialist nurse (X22.072; p = 0.150). Overall conversion rate to breast reconstruction has been 89%.

Conclusions: This data demonstrates that there appears to be no difference between the patient reported outcomes when receiving information from either the specialist nurse or the surgeon. Therefore, a pre-operative nurse led clinic for breast reconstruction can be an effective and acceptable approach for patients seeking this service.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-17-06.
Abstract P4-17-07: Reconstructive Outcomes of Nipple-Sparing Mastectomy: A Five Year Experience
Authors: Guth AA , Blechman K , Samra F , Shapiro R , Axelrod D , Choi M , Karp N , Alperovich M
Published: August 2014

Background: Nipple-sparing mastectomy (NSM) has gained popularity, but remains contoversial as the procedure's reconstructive outcomes and oncologic safety are still somewhat uncertain.

Methods: We retrospectively reviewed the New York University-Langone Medical Center experience with NSM from 2006–2011. Outcomes measured include post-operative complications, breast cancer recurrence, presence of cancer at the nipple-areolar complex, and nipple-areolar complex viability.

Results: Our data include patients who underwent NSM from 2006–2011. In total, the records of 235 (145 prophylactic, 90 theraputic) NSM at NYULMC were reviewed. Our reconstructive dta included all forms of reconstruction, including 144 tissue expanders, 74 microvascular free flaps, 16 immediate implants, and 1 combination latissimus dorsi flap with implant. Mean follow-up time was 19 months. No differences existed between the theraputic and prophylactic breast patients.

The major complication rate of 4.3% (10/235) included 4 intraoperative hematoma evacuations, 1 flap anastomosis revision, and 3 explanted implants. One patient expired 4 months following surgery secondary to progression of disease. The microvascular free flap loss rate for this group was 0. Minor complications in 6.8% of patients consisted of implant exchange for asymmetry, operative revision of partial flap necrosis, intravenous antibiotics for infection, and 1 non-operative hematoma.

In total, 5.9% of nipples were resected due to malignant or premalignant disease. There were 3 positive intraoperative biopsies with 9 additional biopsies positive on final pathology. To date, there have been no recurrences involving the nipple-areolar complex. The viability rate for the remaining nipples was 93.2% with1.7% of nipples undergoing complete necrosis, 3.8% partial necrosis, and 1.3% undergoing epiderolysis.

Conclusions: This experience with NSM demonstrates the in a carefully selected cohort, oncologic safety and reconstructive outcome are comparable to the current standard of total mastectomy.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-17-07.
Abstract P4-17-09: Efficacy and safety of lipomodelling and adipose tissue derived degenerative stem cells(ADRC) for breast reconstruction – Medium term follow up
Authors: Noor L , Bhaskar P , Hennessy C
Published: August 2014

Background: Past and current literature support Lipomodelling as a tool for breast reconstruction. Lipomodelling with Adipose tissue Derived Regenerative Stem Cells dramatically improves the graft survival through both adipogenesis and angiogenesis. Literature regarding safety of this procedure for breast reconstruction is limited. Our aim was to assess the safety and efficacy of ADRC-enriched fat grafts for breast reconstruction.

Material & Methods: A prospective study from September 2008 – April 2012 at a District General Hospital UK including patients operated by two breast surgeons. The indications and the fat grafting procedures used are analyzed (Cytori Celution 800/CRS or Cytori pure graft system). Patients with benign indications were followed for 1 year and those with cancer were followed for 5 years according to regional guide lines with breast imaging.

Results: Out of total 50 patients, 10 had benign diagnosis while 40 had breast cancer treatment. 30 patients had correction after breast conservation, 17 had revision of reconstruction (8 TRAM, 4 LD and 5 implant based reconstruction) while 3 had other procedures. 19/40 had history of breast irradiation as adjuvant treatment after surgery for breast cancer. Median age was 52 years with range 18–72 years. ADRC enriched fat grafting was done in 40 cases and pure graft in10 patients. Graft volume injected was 80–420 mls (average 247 mls). 90% patients are satisfied with outcome of surgery with good to excellent cosmetic outcome. Only 4 patients had noticeable fat resorption, 3 underwent redo grafting. At average follow up of 21 months (1–48 months) no significant complications were seen, imaging showed fat necrosis in 3 and oil cyst in 1 patient though no one required biopsy. No patient developed local recurrence, although 4 subsequently found to have metastatic disease.

Conclusion: We found it a useful, safe and effective technique for breast reconstruction with high patient satisfaction. We recommend a central database of all patients with this procedure to substantiate findings of this study and as recommended by Association of Breast Surgery (ABS) & British Association of Plastic Reconstructive & Aesthetic Surgeons (BAPRAS).

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-17-09.
Abstract P5-01-03: Discordant Estrogen and Progesterone Receptor Status in Breast Cancer
Authors: Hefti MM , Hu R , Knoblauch N , Collins L , Tamimi RM , Beck AH
Published: August 2014

Introduction: Hormone receptor status is used to guide clinical therapy in breast cancer. Estrogen receptor (ER) assays from pathology reports have been shown to be in agreement with ER measured by a centralized laboratory on tissue microarray 87% of the time (Kappa = 0.64); however, little is known of reproducibility within subsets of patients defined by ER/PR status (1).

Methods: We computed percent agreement and Kappa statistics for ER/PR status as reported in pathology reports from Nurse's Health Study (NHS) participants with breast cancer from 1976 to 2000, and as scored by immunohistochemistry (IHC) on tissue microarrays at a central laboratory (n = 2011). Statistics were computed separately for 4 subsets of patients stratified by ER/PR status as defined by pathology reports (ER+/PR+, ER+/PR−, ER−/PR+, ER−/PR−). We also used a curated compilation of publicly available gene expression data sets providing both IHC and microarray data on ER and PR expression (n = 1236).

Results: We observed significant heterogeneity in Kappa values across the four groups of patients, with ER+/PR+ and ER−/PR- showing the strongest agreement, ER+/PR- showing fair agreement, and ER−/PR+ showing no significant agreement: 89.1% of ER+/PR+ cases from medical record were ER+/PR+ by TMA (κ=.60), 69.4% of ER−/PR- cases from medical record were ER−/PR- by TMA (κ=.63), 42% of ER+/PR- cases from medical record were ER+/PR- by TMA (κ=.37), and only 6% of cases of ER−/PR+ cases from medical record were ER−/PR+ by TMA (κ=.06). Using publicly available microarray data, we observed similar results comparing IHC to gene expression data in the same samples. Expression values were scaled across patients, and a patient was classified as positive for the marker by microarray if the scaled expression value was greater than zero. The agreement between IHC data and gene expression-based classification was 50.0% (k = .50), 80.8% (κ=.54), 42.0% (κ=.15), and 7.2% (κ = −.006) for ER+/PR+, ER−/PR−, ER+/PR−, and ER−/PR+, respectively.

Conclusion: ER−/PR+ is by far the most rare and least reproducible subset of breast cancer cases. Given the lack of reproducibility of the ER−/PR+ group and the minimal reported benefit from hormonal therapy in these patients (2), these data question the clinical utility of assessment of PR, particularly in ER− breast cancer.

1. Collins LC, Marotti JD, Baer HJ, Tamimi RM. Comparison of estrogen receptor results from pathology reports with results from central laboratory testing. Journal of the National Cancer Institute. 2008;100(3):218–21. 2. Anderson H, Hills M, Zabaglo L, A'Hern R, Leary AF, Haynes BP, et al. Relationship between estrogen receptor, progesterone receptor, HER-2 and Ki67 expression and efficacy of aromatase inhibitors in advanced breast cancer. Annals of oncology: official journal of the European Society for Medical Oncology/ESMO. 2011;22(8):1770–6.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-01-03.
Abstract P5-01-05: Could c-myc amplification replace Cahan's criterias to discriminate secondary from primary angiosarcoma of the breast?
Authors: Laé M , Hamel F , Hadj-Hamou S , Malfoy B , Kirova YM
Published: August 2014

Background: Angiosarcomas (AS) are a relatively rare histological subtype of sarcomas. Despite their rarity, AS display remarkable clinical heterogeneity. These tumors can occur in any location in the body, but the breast AS are important part of these tumours. Cahan et al. defined the criteria for the diagnosis of radiation induced sarcomas (RIS), used since 1948: i) prior history of RT; ii) asymptomatic latent period of several years; iii) the occurrence of a sarcoma within a previously irradiated field; iiii) histological confirmation of sarcomatous nature of the post-irradiation lesion.

Purpose: The aim of this study is to show a new biological data which can help us to recognize these rare tumors.

Material and Methods: Forty-one breast AS were studied (pathological review, clinical and follow-up information obtained), as well as the transcriptome signatures of the radiation tumorigenesis. For all RIS, the patients' radiotherapy plans and hospital records were reviewed and their radiation related nature was confirmed if they respected the classic Cahan's criteria. Interphase FISH was performed by hybridization of probes covering C-MYC (chromosome 8q24.21) and CEP8 on tissue sections from each of the forty-one tumors.

Results: Among forty-one breast AS, thirty one were secondary tumors and ten primary tumors. Amplification (5 to 20 fold) of the MYC oncogene was found in all breast secondary AS (31 cases) but in none of the 10 primary AS except one. The relationships between clinical, pathological and biological features are studied. These data point the pathways preferentially involved in the pathogenesis of secondary AS of the breast and may provide the basis for an additional targeted therapy.

Conclusion: The presence of c-myc amplification on biopsy or surgical specimen represents an important additional tool to discriminate secondary from primary angiosarcoma of the breast when radiotherapy data are not available.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-01-05.
Abstract P5-01-06: Differences in FGF1 and FGFR2 expression in BRCA1-associated, BRCA2-associated, and sporadic breast carcinomas
Authors: Vos S , van der Wall E , van Diest PJ , van der Groep P
Published: August 2014

Introduction. In contrast to BRCA1-associated breast cancer, a distinctive phenotype for BRCA2-associated carcinomas has not been identified yet as there is no clear distinction between BRCA2- and non-BRCA mutation related or sporadic carcinomas. Recently, studies suggest overexpression of fibroblast growth factor 1 (FGF1) and fibroblast growth factor receptor 2 (FGFR2) in BRCA2 related cancers. The aim of the study was therefore to investigate whether there is differential expression of FGF1 and/or FGFR2 between BRCA2 related and sporadic and BRCA1 related cancers. This would reveal the usefulness of FGF1 and FGFR2 immunohistochemistry in daily pathology practise.

Method. Invasive breast carcinomas of 33 BRCA1 and 22 BRCA2 germline mutation carriers and a tissue microarray containing 104 sporadic invasive breast carcinomas were immunohistochemically stained for FGF1, FGFR2, estrogen receptor (ER), progesterone receptor (PR), HER2, epidermal growth factor receptor 1 (EGFR), cytokeratin (CK) 5/6 and CK14.

Results. FGFR2 expression was seen in 68.2% and 79.0% of BRCA2-associated and sporadic carcinomas respectively, in contrast to 22.6% of BRCA1-associated tumors (p = 0.000). FGF1 expression was seen in 72.7% of BRCA2-associated carcinomas and in 45.2% and 41.8% in BRCA1-associated and sporadic carcinomas, respectively (p = 0.032).

Conclusion. FGFR2 expression differs significantly between BRCA1- and BRCA2 associated breast carcinomas but not between BRCA2 and sporadic cancers. FGF1 expression differs significantly between BRCA2-associated and sporadic carcinomas and could be used as a BRCA2-specific biomarker.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-01-06.
Abstract P5-01-10: Clinical-pathological features and outcomes of Invasive lobular (ILC) vs Invasive ductal (IDC) breast cancer (BC): a mono-institutional series.
Authors: Ferro A , Eccher C , Triolo R , Caldara A , Di Pasquale MC , Russo LM , De Carli NL , Cuorvo LV , Barbareschi M , Gasperetti F , Berlanda G , Pellegrini M , Moroso S , Galligioni E
Published: August 2014

Purpose: The aim of our study was to investigate different clinico-biological behavior associated to ILC compared to IDC evaluating implications on survival outcomes

Methods: We analyzed data from 3749 cases of IBC treated from 1995 to 2008 and categorized as having ILC, IDC and mixed/other. Associations between clinical-pathological variables and the ILC/IDC histotype were assessed using a χ2 test. Log-rank test and Cox regression model were performed to evaluate the impact of hystologic types on overall survival (OS), Event Free Survival (EFS) and Post-Progression Survival (PPS).

Results: We identified 445 (12%) ILC, 3021 (80.5%) IDC, 149 mixed (ductal-lobular) BC (3.9%) and 134 other hystotypes (3.6%). Median age was 61 (25–97) years. Compared with IDC, ILC occurred significantly (p < 0.001) more likely in older age, larger in size (T≥2: 46 vs 34%) with frequent axilla involvement (43 vs 37%). It was associated with better differentiated tumors usually presenting low ki67, high level of ER expression and HER2 negative status. Mastectomies were more frequent (45%) in ILC than in IDC (37%). As ILC showed higher ER expression rates, adjuvant hormonal (± previous chemo) therapy was more frequently given to them than IDC (77 vs 64%). At a median follow up of 77 (0–272) months, there were not significant differences in EFS (81.4 vs 82.1%, p = 0.7) and OS (82.8 vs 84.6%; p = 0.19) between ILC vs IDC. Relapses, contralateral and second tumors were 65 (15%), 9 (2%) and 22 (5%) in ILC vs 404 (13%), 84 (2.8%) and 174 (5.7%) in IDC. Local recurences were 16 (3.6%) vs 175 (5.7%) in ILC vs IDC; preferential sites of distant relapses were similar in both histotypes. Median time to first event was 38.3 in ILC vs 35.23 months in IDC. PPS was 16.5 m (0–100) in ILC and 22.2 m (0–187) in IDC. ILC showed worse prognosis than IDC within luminal A (86.9 vs 93.5%; p = 0.003), C (70.4 vs 88.5%; p = 0.028) and in triple negative subtypes (50 vs 73.1%; p = 0.021). No difference in OS was seen for age, size, hormonal and nodal status, except in N >3 ILC pts, in whom a trend of worse prognosis (55.6 vs 60.2%) was observed.

Conclusions: Despite the quite favorable biological pattern, ILC did not show a better outcomes than IDC.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-01-10.
Abstract P5-01-12: Over- and Undergrading of Breast Cancer on Core Biopsies in Comparison to Surgical Specimens
Authors: Decker T , Focke CM , Gläser D , Finsterbusch K
Published: August 2014

Background: In numerous studies histological grade (HG) remained an independent prognostic factor for ER positive tumours even after the inclusion of gene signatures in the multivariate models. Moreover, grade 3 is judged as clear argument in favour of chemotherapy. Therefore, there are many reasons to provide patients and doctors with HG as important prognostic and predictive information already preoperatively. To evaluate the relevance of histological grading (HG) based on core biopsies (CB) for clinical decision making in breast cancer (BC) we evaluated the concordance with HG from surgical specimen (SSP) and the reasons for under- or overgrading.

Methods: CB and related SSP of 398 BCs were prospectively graded according to the Nottingham grading system (SSP: 65 G1, 162 G2 and 171 G3). CB/SSP agreement rates and positive predictive values (PPV) of CB based HG were calculated. Rates of over- and underestimation of glandular differentiation (GD), nuclear pleomorphism (NP) and mitotic activity (MA) were calculated.

Results: CB/SSP agreement rates came out with 95% for G1, 73% for G2, and 56 % for G3. The PPVs of CB based HG were 56% for G1, 61% for G2 and 100% for G3. The overgrading and undergrading rates on CB were 1% and 37%, respectively. Main causes for undergrading in CB were underestimated MA (40%) and a combination of underestimated NP and MA (32%).

Conclusions: Whereas overgrading on CB is an exception, undergrading derives largely from underestimation of proliferation. G3 assessed on CB came out with the highest PPV, providing a reliable base for preoperative decisions i.e. about primary chemotherapy. Reversely, because of the relative low PPV of G1 on CB one has to be aware of potential upgrading on surgical specimen later on.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-01-12.