bluuebunny/crossref_metadata_2025 huggingface dataset:
P2-13-07: Prevalence of Germline BRCA1 and BRCA2 Deleterious Mutations in Brazilian Patients with High-Risk of Breast and Ovarian Cancer.
Authors: Diz MDPE , Escobar KA , Guindalini RSC , Pasini FS , Snitkoviski ML , Maistro S , Hoff PMG , Federico MHH
Published: June 2012

Background: Germline mutations in the BRCA1/2 genes account for the majority of hereditary breast ovarian cancer (HBOC). Distribution and prevalence of clinically relevant mutations in BRCA1/2 differ among different populations. All of the Brazilian studies published to date have not performed complete sequencing of both genes, restricting their analyses to selected exons. In addition, a highly heterogeneous mutation spectrum was observed. The lack of data concerning the prevalence and profile of BRCA1/2 deleterious mutation and the appropriated screening criteria for DNA sequencing in the Brazilian population complicates the design of screening strategies.

Objective: To accurately determine the contribution of BRCA1/2 germline mutations in a well characterized sample of Brazilian breast and ovarian high-risk pts.

Methodology: A total of 73 unrelated pts attending a Brazilian public hospital from September 2005 to July 2006, with HBOC risk ≥10% according to Frank, Evans or BRCAPRO algorithms, underwent complete sequencing and MLPA analysis of BRCA1/2 genes. Demographic data and tumor pathological features were extracted from prospectively registered medical records.

Results: Mean age, median of cancer cases in families and median score by Frank, Evans and BRCAPRO algorithms were respectively 48y (24-78), 4 (0-13), 11.2 (0-56,3), 13.4 (0,1-100) and 16 (2-75). A total of 79 unknown clinical significance mutations were identified: 44 in BRCA1 and 35 in BRCA2. Known deleterious mutations were identified in 8 pts. Four in BRCA1: R71G at exon 5, 5382insC at exon 20 (2 patients) and R1751X at exon 20; and four in BRCA2: R2318X at exon 13, R3128X at exon 25, 5844del5 and 6633del5 at exon 11. Several polymorphisms were found in all pts. No mutation was detected by MLPA technique. One novel frameshift deleterious mutation in BRCA2: 6610insTT at exon 11 which results in a stop codon was detected in a breast cancer patient and in four of her relatives from a family with high-risk of HBOC. Taking into account the novel mutation, the prevalence of BRCA1/2 mutation in high-risk pts in our cohort is 12,3%. Pts characteristics presented in [table 1]. Conclusion: To the best of our knowledge, the study represents the first report of the complete sequencing and MLPA analysis of BRCA1/2 genes in large Brazilian series of HBOC high-risk pts. The prevalence of germline mutations found in the present study was similar to the reported by other studies examining high-risk populations.

B1=BRCA1; B2=BRCA2; BC=breast cancer; IDC=invasive ductal carcinoma; MC=medullary carcinoma; ILC=invasive lobular carcinoma; HR=hormone receptor; (b)=bilateral, N/A=not available; N/C=never had cancer; pos=positive; neg=negative, ind=indeterminate

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-13-07.
P2-13-09: First Statewide Experience with Telephone Delivery of Cancer Genetic Counseling.
Authors: Pruski-Clark J , Trivedi A , Kelle S , Rebecca S
Published: June 2012

Background: National guidelines and multiple professional medical societies recommend genetic counseling as the standard of care for women with a personal and/or family history suggestive of a hereditary cancer syndrome. In addition, the ability to provide risk assessment and genetic counseling is a requirement for accreditation of breast centers by organizations such as the National Accreditation Program for Breast Centers (NAPBC) and the Commission on

Cancer. However, there is clear evidence that this standard is not being achieved. Many individuals are undergoing genetic testing for these syndromes without adequate pre- and post-test counseling and, on the other hand, many individuals who are appropriate for genetic testing are not being identified and referred for genetic counseling and therefore not receiving potentially life-saving genetic information and services. A number of factors have been identified as contributors to these poor public health outcomes, including a lack of available genetic counseling services due to a limited number of trained genetics professionals and their limited geographic distribution. Research has demonstrated the effectiveness of cancer genetic counseling delivered by telephone, but to date, almost no real-world experience has been reported. We provided statewide access to board-certified genetic counselors via telephone in Michigan beginning in February 2010 and report our experience with the first 200 patients at risk for hereditary breast and ovarian cancer.

Materials and Methods: Baseline data were analyzed for all Michigan patients undergoing telephone genetic counseling through Informed Medical Decisions since service delivery began in February 2010. Variables include demographics, geographic location, personal cancer history, family cancer history, Gail risk and test appropriateness criteria.

Results: Analysis has been completed on the first 200 patients referred for consideration of hereditary breast and ovarian cancer. Outcomes include testing, results and, where applicable, reasons testing was not pursued, patient and provider satisfaction, as well as trends over time in patient volumes, providers using the service and uptake by geographic location.

Conclusion: Based on statewide experience in Michigan, telephone cancer genetic counseling is a viable method for service delivery in the real world. The Michigan experience can serve as a cost-effective model for improving genetic services in other locations with limited access to genetic experts.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-13-09.
P2-13-10: Detection, Visualization and High Resolution Physical Mapping of Large Rearrangements by Molecular Combing in the Hereditary Breast Cancer Genes BRCA1 and BRCA2.
Authors: Ceppi M , Roleau E , Cheeseman K , Thomas A , Briaux A , Lefol C , Walrafen P , Bensimon A , Lidereau R , Conseiller E
Published: June 2012

The BRCA1 and BRCA2 genes are involved, with high penetrance, in breast and ovarian cancer susceptibility. About 2% to 4% of breast cancer patients with a positive family history who are negative for BRCA1 and BRCA2 point mutations can be expected to carry large genomic alterations (deletion or duplication) in one of the two genes, and especially BRCA1. However, large rearrangements are missed by direct sequencing.

Molecular Combing is a powerful FISH-based technique for direct visualization of single DNA molecules, allowing the entire genome to be examined at high resolution in a single analysis. We have developed a novel genetic test based on Molecular Combing. For that purpose, we designed specific BRCA1 and BRCA2 “Genomic Morse Codes” (GMC), also covering the non-coding regions and including large genomic portions flanking both genes. We developed a measurement strategy for the GMC signals, and validated our approach by blindly testing 10 breast cancer patients with a positive family history and 10 control patients. Large rearrangements, corresponding to deletions and duplications of one or several exons and with sizes ranging from 3 kb to 40 kb, were detected on both genes, including the characterization of 4 new mutations (for BRCA1: Del ex 3, Del ex 24 and Dup ex 3; for BRCA2: Dup ex 17–20). The identified mutations confirmed the results obtained with high-resolution zoom-in aCGH (11 k) in the same patients, with a resolution in the 1–2 kb range. Importantly, the developed GMC allowed to unambiguously localize several tandem repeat duplications on both genes, and to precisely map large rearrangements in the problematic Alu-rich 5'-region of BRCA1.

We propose the developed Molecular Combing genetic test as a valuable tool for the screening of tandem repeat duplications, CNVs, and other complex rearrangements in BRCA1 and BRCA2, such as translocations and inversions, to be combined in clinical settings with an essay that allows the detection of point mutations. We see the main application of the developed molecular diagnostic tool as a predictive genetic test. However, we envisage to extended the application of the developed tool as a companion diagnostic test, for instance in the screening of BRCA-mutated cells in the context of the development of PARP inhibitors. Thus, the genetic test may be applied not only to clinical blood samples, but also to circulating cells and heterogeneous cell populations, such as tumor tissues.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-13-10.
P2-14-10: Are There Variations in Invasive Tumour Characteristics between Different Ethnic Groups?
Authors: Hariri B , Lo M , Gandamihardja T , Lewis J , Hogben K
Published: June 2012

Introduction: Studies have shown that ethnic minorities with breast cancer are more likely to present at a younger age and with more aggressive tumours. The aim of this study was to examine the variation in tumour characteristics and surgical outcomes in different ethnic groups in our breast unit over a 12-month period.

Methods: A retrospective study was performed on all patients with a new diagnosis of breast cancer, either screen-detected or symptomatic, between January to December 2009. Using our Trust databases, data on patient demographics, tumour characteristics, and ethnicity were collected. Where ethnicity was not documented, patients were contacted by telephone to complete the database. Those unable to be contacted were excluded from the study. Other exclusion criteria include those with recurrent ipsilateral breast cancer.

Results: A total of 270 patients (265 females) were included in our study, of which 235 (87%) had invasive cancers (ductal carcinoma, lobular carcinoma, tubular carcinoma, mucinous carcinoma, cribriform carcinoma, papillary carcinoma, sarcoma) and the remaining 35 patients (13%) had non-invasive cancers (ductal carcinoma in-situ, lobular carcinoma in-situ, papilloma, columnar cell hyperplasia).

We were unable to contact 23 (8.5%) patients to ascertain their ethnicity, and therefore these have been excluded from our results.

Table 1. Tumour characteristics and surgical intervention in patients with invasive breast cancer in 2009

Conclusion: We found that the age of breast cancer presentation was lowest in Black and Asian patients (mean age 52 years and 54 years, respectively), compared to White (mean age 59 years). Furthermore, compared to white patients, tumours in Asian patients were larger (62.5% vs 47.2%), of higher grade (83.3% vs 75.2%), more likely to be ER negative (16.7% vs 12.4%), and tended to be lymph node positive (41.7% vs 34.2%). These may explain the higher mastectomy rate in Asian patients (n=12, 50%).

The reason for the younger presentation age in the ethnic Asian group is unclear. However, it is possible that their cancer may have different tumour biology. Other studies have suggested reasons such as birth cohort effect and obesity.

Reflecting the United Kingdom's population the majority of patients that present to our breast unit are White and the number of Asian patients remains small. An increase in the sample size may strengthen our results.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-14-10.
P2-15-03: Nipple-Sparing Mastectomy for Breast Cancer in Japanese Experience: An Assessment from Long Follow-Up Data of Complication and Cancer Control in 806 Patients.
Authors: Sakurai T , Sakurai T , Umemura T , Jinta E , Suzuma T , Yoshimura G
Published: June 2012

[Introduction] Mastectomy has been conducted in general for cases in which breast conservation is inapplicable. Since Nipple-sparing Mastectomy (NSM) conserves nipple-areola, it is not only more advantageous in an aspect that nipple-areola reconstruction isn't required in case of breast reconstruction compared with mastectomy but also significantly meaningful because the sensation of nipple-areola is preserved in about 70% cases by skin flap preparation based on thick flap method we have adopted. On the other hand, NSM is controversial relating to complication of surgery and recurrence as well.

[Objective] We've made (1) review of safety in NSM surgical technique, (2) discussion over recurrence and prognosis comparing with those in mastectomy, and (3) consideration of performance in immediate reconstructions.

[Result] (1) Of all cases of NSM, the number of cases in stage 0, 1, 2A, 2B, 3 and 4 was 21, 305, 239, 123, 112 and 6 respectively. During 104 months of follow-up period in average, total of seven complication cases (0.9%) were observed, including two flap necrosis cases and five postoperative bleeding cases, but no nipple necrosis case was recorded. Although nipple-areola recurrence rate (%) in stage 0, 1, 2A, 2B and 3A was 0, 2.9, 4.6, 2.4 and 5.3 respectively, prognosis of nipple-areola recurrence cases was good showing no difference between stages (OS: 60M; 93%, 100M; 84%). Skin flap recurrence rate (%) in stage 0, 1, 2A, 2B and 3 was 0, 3.2, 3.3, 4.0 and 14.2 respectively, and prognosis of skin flap recurrence cases was significantly worse in stage 2B and 3 compared with that in stage 1 and 2A (p < 0.001).

(2) We analyzed local recurrence rate, recurrent free survival and overall survival between 806 of NSM cases and 200 of mastectomy cases which had been performed during the same period, and the result showed no significant difference in those rates between NSM and mastectomy cases.

(3) Infectious complication was observed in one out of 18 immediate reconstruction cases using free dermal fat graft. Among 124 immediate reconstruction cases using implant, complications were observed in five postoperative bleeding.

[Conclusion] NSM was excellent in cosmetic aspect showing equivalent results in local recurrence rate and prognosis compared with those in mastectomy cases. Besides, patient's satisfaction was also higher in those who had had NSM alone without reconstruction. Our long term follow-up data shows that NSM may be considered as an alternative option for mastectomy in cases in which breast-conserving surgery is inapplicable in breast cancer patients.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-03.
P2-15-05: Excision of the Primary Tumour in Patients with Metastatic Breast Cancer – Will E2108 Provide the Definitive Answer?
Authors: Samiee S , Berardi P , Bouganim N , Vandermeer L , Arnaout A , Mirsky D , Dent S , Caudrelier J-M , Chasen M , Clemons M
Published: June 2012

Background: Approximately 10% of new breast cancer patients will present with overt synchronous metastatic disease. Controversy exists about the optimal local management of these patients. While several series suggest that removal of primary tumour is associated with a survival benefit, the retrospective nature of these studies raises considerable methodological challenges. We decided to evaluate the experience at our centre around the impact of surgery in patients with synchronous metastasis.

Method: Case records of all patients seen with primary breast cancer and concurrent distant metastases between 2005 to 2007 were reviewed. Demographic and treatment data was collected. The study endpoints compared both overall survival and symptomatic local progression rates between patients who had breast surgery and those who did not.

RESULTS: 111 patients were identified. Median follow-up 40 months (0.6-71 months). Patients were divided into two groups: those patients who underwent breast surgery (n=48; 29/48 had surgery immediate prior to metastatic diagnosis) and those that did not have surgery(n = 63). The surgical group were less likely to present with T4 tumours (20% vs 36%), N3 nodal disease (8% vs 19%) and visceral metastasis (67% vs 73%)when compared with non-surgical group. Improved overall survival (49 months vs 33 months; p=0.01) and less symptomatic local progression rates ( 15% vs 43%, p < 0.001 ) were seen in the surgical group compared to the non-surgical group.

CONCLUSIONS: The optimal local management of patients with metastatic breast cancer is unknown. Despite the surgery group demonstrating an improved overall survival and symptomatic local control, this group had less aggressive disease at presentation. These results confirm the need for prospective randomized studies. E2108, an ongoing Phase III Trial, was designed to assess the effect of breast surgery in metastatic patients responding to first line systemic therapy. If excision of the primary tumour is associated with a survival benefit, then the pre-selected subgroup of patients that have responded to initial systemic therapy is the desired population to put this hypothesis to test.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-05.
P2-15-07: The Need for Additional Surgeries to Adequately Excise Early Breast Cancers May Have a Negative Impact on Local Recurrence.
Authors: Warburton R , Alriyees L , Wang DY , Wong SL , Leong W
Published: June 2012

Background: Breast conservation surgery (BCS) is considered the standard of care for the treatment of early stage breast cancer (ESBC, AJCC stage 1 and 2). 20 to 50% of patients will require further surgery for positive or close margins. There is recent data suggesting that re-operation can have a negative impact on local and distant recurrences. Our aim is to examine the effects of multiple surgeries to obtain adequate margins on breast cancer recurrence, metastatic disease and survival.

Methods: We reviewed a prospectively maintained breast cancer database at the University Health Network and included all women who had BCS for their first diagnosis of ESBC between January 2004 and December 2007. Patients with neoadjuvant chemotherapy were excluded. We collected patient demographics, surgical pathology, adjuvant therapy and follow up outcome data, which included local recurrence, distant recurrence, cancer-specific survival and overall survival. Clinical and pathologic features were compared using chi-square analyses. Patients who had one lumpectomy were compared to those who had multiple surgeries by using Kaplan-Meier survival curves and log rank test.

Results: Of a total of 744 patients (8 patients had bilateral cancer) 577 (77.6%) had one lumpectomy only (Group 1). 167 (22.4%) patients required further surgery (group 2 = LR+LM+LRM): 83 (11.1%) had a re-excision (LR), 69 (9.3%) had mastectomy (LM) and 15 (2%) had a re-excision followed by a mastectomy (LRM). Thus, a total of 85 (11.4%) patients had mastectomy to achieve adequate margins. All clinicopathologic factors and adjuvant systemic treatments were similar between the two groups except for age and use of adjuvant radiotherapy, which was related to that fact that many of those in group 2 had mastectomy. We observed a difference in disease-free survival favoring patients with lumpectomy only (group 1–3.4% vs. group 2–8.1%, p= 0.01) but there was no difference in distant metastasis (4.5% vs. 5.6%, p=0.56), cancer-specific survival (97.6% vs. 95.6%, p=0.20) and overall survival (6.9% vs 6.3%, p= 0.76) at a median follow up of 4.54 years.

Conclusion: Despite having similar stage, grade, receptor status and adjuvant systemic therapies, having multiple surgeries for primary breast cancer appeared to be associated with decreased disease-free survival but had no difference in rates of distant metastatic disease, cancer-specific survival and overall survival.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-07.
P2-15-10: Do Patients with Incurable Advanced Breast Tumor and Distant Metastasis Derive Any Benefit from Primary Tumor Resection?
Authors: Takahashi M , Shibasaki S , Jotoku H , Watanabe K-I
Published: June 2012

Background

Metastatic breast cancer (MBC) is considered incurable. Surgical removal of primary tumors has not been established as a standard treatment for MBC because it is generally accepted that local therapy provides no survival advantage once metastases have occurred. Additionally, tumor excision may further stimulate metastasis.4 Therefore, primary tumor resection in patients with MBC is usually only applied as a palliative treatment for symptomatic wound complications such as bleeding, ulcer formation, unpleasant smell, and purulent discharge. In recent years, however, some retrospective studies have reported advantages of debulking surgery in terms of improving patient outcome. We retrospectively analyzed the surgical benefits and prognostic factors for patients with MBC who were treated at our center.

Methods: We retrospectively reviewed individual medical records from the Hokkaido Cancer Center. In this study, incurable advanced breast cancer is defined as the presence of a tumor, larger than 5 cm, and shows either (invasion to chest wall or skin or is an inflammatory carcinoma) and at least one metastatic site, including distant lymph nodes, bone, or visceral organs (lung, pleura, mediastinum, liver, and brain) at diagnosis. Between January 2000 and June 2010, 92 women were diagnosed with incurable advanced breast cancer at our institute. The effect of surgical treatment on survival was evaluated. Patient demographics and tumor characteristics were also investigated.

Results: Thirty-six patients had surgery for resection of primary tumors. There were no substantive differences between individuals, or between tumor characteristics, for patients who underwent surgery versus patients who did not. The median survival time for surgically treated patients was 25.0 months versus 24.8 months for patients who did not undergo surgical resection (P=0.352). Only three patients relapsed within three months of surgery. For the remaining majority of patients, primary tumor resection gave some relief from the often severe symptoms that come from harboring a large tumor for an extended time. In univariate and subsequent multivariate analyses of predictive indicators, a diagnosis of triple-negative breast cancer and/or metastasis to more than three sites was significantly associated with a severe prognosis.

Conclusion: Primary tumor resection failed to prolong overall survival times in patients with incurable advanced breast cancer that was greater than 5 cm. However, surgery did improve the quality of life in patients who were expected to have a relatively long prognosis.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-10.
P2-15-11: Outcomes of Corrective Procedure with Vicryl Mesh as an Oncoplastic Surgery of the Breast.
Authors: Lim YA , Lee YO , Kim JH , Kim HS , Kang HJ , Kim LS , Hallym Sacred
Published: June 2012

Background: Both cosmetic and oncologic outcomes are becoming more important for breast cancer patients. Breast-conserving surgery (BCS) has an acceptable cosmetic result compared with mastectomy, but BCS is also associated with cosmetic failure. In this study, we evaluated the cosmetic outcome of reconstructive surgery with the absorbable implant vicryl mesh after BCS compared with the outcome of BCS alone.

Methods: From May 2007 to December 2009, 101 patients were involved in this study at Hallym University Sacred Heart Hospital. We used absorbable implants made of folding vicryl mesh and wrapped them with Interceed. In 79 cases, BCS with vicryl mesh implantation was performed; in the other 56 cases, only BCS was performed. Patient satisfaction with cosmetic outcomes was evaluated. We also analyzed other factors that affected cosmetic outcomes, including patient ages, body mass indices, tumor locations, and removed breast tissue.

Results: In the vicryl mesh implantation group, 65 of 79 patients (82.3%) were satisfied; in the BCS-only group, 24 of 56 patients (43%) were satisfied (P < 0.05). In the vicryl mesh implantation group, patient ages, body mass indices, and removed breast tissue did not affect cosmetic outcomes. When the tumor was located in the upper outer quadrant, the patients were more satisfied (P < 0.05). Conclusions: Reconstructive procedures with vicryl mesh are simple, safe, and less expensive than other plastic reconstruction techniques. This study suggests that the procedure was superior to BCS alone in cosmetic outcomes. We believe that the procedure could become a favorable technique in oncoplastic surgery.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-11.
P2-15-12: Management Strategy of Early-Stage Breast Cancer Patients: With or without Axillary Lymph Node Dissection.
Authors: Yamamoto D , Tanaka K , Tsubota Y , Yosida H , Kanemastu S
Published: June 2012

Background: The sentinel lymph node (SLN) biopsy has steadily replaced axillary lymph node dissection (ALND) for staging clinically node-negative breast cancer. However ALND remains the standard management of the axilla when a tumor-positive sentinel lymph node (SLN) is identified. The aim of this study was to evaluate the ALND in local, distant recurrence, and overall survival (OS) in breast cancer patients.

Methods: We identified 350 patients with breast cancer (clinically T1/T2N0M0) from the prospective database from five institutions from July 1999 and April 2004. All patient age ranged from 26 to 81 (median 49) years. All patients underwent mastectomy or breast conserving surgery (BCT) combined with either ALND or no ALND. Criteria of negative ALN metastasis are that minor axis of ALN is under 5 mm on CT images and fat tissue in the hilum of ALN does not disappear on ultra-sound images. In the case that hormone receptor expression is positive, pt was administered for 5 years. In the case of T1c or T2 under 70 years old, neoadjuvant and/or adjuvant anthracycline-based chemotherapies were administered. After surgery, patients without ALND/with ALND received tangential irradiation at the region of breast. ALND and no ALND groups were compared for incidence of local, regional, distant recurrence, and overall survival. Results: Patients with ALND (n=350) were compared with no ALND group (n=126). There were significant differences in primary tumor size, histology, nuclear grade, presence of LVI, ER/PgR/HER2 status between the two groups. Five years OS was 97.9% in ALND group, it was 98.0% in no ALND group (p>0.01). Further there was no significant difference between two groups in local, regional, and distant recurrence.

Conclusions: These results indicate that ALND is omissible for cT1/T2N0M0 breast cancer by a combination of hormone therapy, neoadjuvant/adjuvant chemotherapy, and irradiation.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-12.
P2-16-03: Outcomes of Nipple-Sparing Mastectomy (NSM) and Immediate Reconstruction.
Authors: Chidester JR , Olson JR , Poruk KE , Marengo JJ , Matsen CB , Neumayer L , Agarwal J
Published: June 2012

Background

Nipple-sparing mastectomy (NSM) is the surgical removal of breast tissue that preserves the entire skin envelope including the nipple areola skin (NAS). We report our experience performing NSMs and immediate breast reconstruction for both high-risk breast cancer treatment and prophylaxis over a six-year period at The University of Utah and Huntsman Cancer Hospital.

Methods: A retrospective chart review was performed on patients undergoing NSM from April 2005 - April 2011. Data collection included: patient demographics, oncologic details, surgical information (including reconstruction timing and type), and complications (infection, hematoma, seroma, skin necrosis, NAS complication, skin flap loss, premature expander exchange/removal, and capsular contracture).

Results: 130 patients underwent 205 NSMs. Of these, 106 (81.5%) patients received mastectomy treatment for cancer while 24 (18.5%) patients were prophylactically treated. 102 NSMs (49.8%) were on breasts with biopsy-proven cancer, while 103 (50.2%) NSMs were on breasts for prophylaxis. All patients were female with a mean age of 44.7 years (range, 16–82 years). 119 (92.2%) patients were Caucasian, 3 (2.3%) were Asian, and 1 (0.8%) was Hispanic. The mean weight was 65.2 kg (range, 42.8 - 98.8 kg) and BMI (n=106) was 23.7 kg/m2 (SE±0.4). 14 (10.9%) and 12 (9.3%) of the patients were known to have a BRCA1 and BRCA2 mutation, respectively. Two (1.6%) patients had a p53 mutation. 172 (83.5%) of the nipples were spared via an 8 cm incision lateral to the midpoint of the areola, while 5 (2.4%) of the incisions were made along the IMF. The remaining 28 (13.7%) incisions were made by other techniques. 201 (98.0%) breasts were immediately reconstructed with tissue expanders (193 went on to implant reconstruction and 8 underwent autologous tissue reconstruction). 4 (2.0%) breasts received delayed reconstruction. Positive margins were found in 15 (7.3%) of 205 breasts. 60 (58.8%) of 102 cancerous breasts that underwent NSM were Stage 0-I, 35 (34.3%) were Stage II and the remaining 8 (7.8%) were Stage III - IV. Complications by case (Table 1) and by breast (Table 2) are shown below.

Conclusion: When comparing NSMs in both patients and individual breasts with cancer to patients and breasts treated for prophylaxis, there is no significant difference in complication rates by case or breast, except for the capsular contracture rate, which was significantly higher in breasts treated for cancer. Overall, complication rates are low in both cases of cancer and prophylaxis; this demonstrates that NSM and immediate reconstruction is a highly effective method of treatment for both groups.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-16-03.
P2-16-08: Expander-Implant-Reconstruction – Aesthetic Outcome and Patients' Satisfaction in a 10-Year-Period.
Authors: Kern PA , Zarth F , Rainer K , Scherag A , Mahdi R
Published: June 2012

Background. Breast reconstruction after mastectomy is gaining increasing significance avoiding the post-mastectomy-trauma and providing the patients with a normal body image after breast cancer survival. This study was conducted to investigate the patients’ characteristics and comorbidities in correlation with the surgical outcome of expander-implant-reconstruction after mastectomy. Patients’ satisfaction with the surgical result and self-perception as well as their partner interaction were also analyzed in their dependance of these patient-related data.

Methods. In this large retrospective cohort study 258 women were enrolled with expander- and/or implant-reconstruction in a single-institution-setting of a 10-years-period (2000-2009). Patient's satisfaction with the result of surgery was evaluated by questionnaires and interviews and patient-related data were retrieved like BMI, smoking, pre-existing diseases and chemo- and radiotherapy, the differentiation between one-stage/two-stage reconstruction, immediate/delayed reconstruction, antibiotics and complications (secondary bleeding, pain, capsular contracture, implant rotation, etc.). Finally, the patients’ interaction with their partners and their adhaerence to their decision for reconstruction was investigated. For explorative statistical analyses we used standard univariate methods appropriately for the scale level of the variables (e.g. Fishers exact tests for n x m Tables or exact Wilcoxon Mann Whitney tests to compare two distributions) and applied a significance level a of 5% to each test.

Results: BMI and patients’ satisfaction with the aesthetic result was inversely correlated (p=0,004) and a negative self-perception had a negative impact on interaction with the partner (p<0,001) after breast reconstruction. BMI was positively correlated with the loss of the implant (p=0,005). Further comorbidities led to worse patients’ satisfaction in rating of the aesthetic results.

Conclusion: Patients characteristics like obesity and other comorbidites are associated with lower patients’ satisfaction with the surgical outcome after expander-implant-breast reconstruction. A decrease of satisfaction is detectable after expander-implant reconstruction within years compared to autologous reconstruction. These results should be taken into consideration for counselling of patients opting for breast reconstruction after mastectomy. This is to our knowledge the largest single-institution study evaluating the patients’ satisfaction with implant-reconstruction after breast cancer treatment and comparing the outcome with various patient characteristics giving a rationale for selection of the optimal reconstructive method.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-16-08.
P2-16-15: Oncological Safety and Survival Rate According to Reconstructive Surgery in Advanced Breast Cancer after Neoadjuvant Chemotherapy.
Authors: Kim WW , Lee JJ , Nam KH , Jung JH , Chae YS , Yang JD , Lee YH , Park HY
Published: June 2012

Purpose: Oncoplastic surgery has received attention according as the incidence of breast cancer is rising and quality of life including cosmetic result after surgery is regarded as important. The aim of this study is to compare combined reconstructive surgery with standard surgery regarding to oncological safety and survival rate in advanced breast cancer after neoadjuvant chemotherapy (CTx).

Method: Thirty-seven patients underwent neoadjuvant CTx and surgery with advanced breast cancer were analyzed from September 2007 to March 2010. Group A (n=12) received combined reconstructive surgery, group B (n=25) had standard surgery.

Results: There were no differences in age, size, metastatic LN, stage, ER/PR/Her-2 status, recurrence, metastasis and death between group A and B. Patients with good response in neoadjuvant chemotherapy (26 cases (72.9%)) had CTx-operation-radiation therapy (RTx), cases with poor response (10 cases (27.1%)) underwent CTx-RTx-operation. There was significant difference in order of treatment, eight patients among group A(66.6%) had CTx-RTx-operation, 22 cases in group B(88.0%) received CTx-operation-RTx (p=0.006). Mean follow up period was 22 months, 2 patients (5.2%) experienced local recurrences, 11 cases (34.3%) diagnosed with distant metastasis, and 4 patients (10.5%) expired with breast cancer.

Conclusion: Advanced breast cancer with poorly responded in neoadjuvant CTx could be actively treated with sequential CTx-RTx-reconstructive surgery. Combined reconstructive surgery was oncologically safe operation in advanced breast cancer.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-16-15.
P2-18-03: Systemic Adjuvant Treatment of T1a and T1b N0M0 HER2+ Breast Carcinomas; an AERIO/UNICANCER Study.
Authors: Peron J , Vano Y , Frenel J-S , Wassermann J , Albiges L , Rodrigues MJ , Cottu PH
Published: June 2012

Background: Trials have shown benefit of adjuvant trastuzumab (TZM) for node-positive (N+) or T1c+ HER2−positive breast carcinomas.

Methods: Retrospective series in 6 french cancer centers from 2000 to 2010 of T1abN0M0 HER2 positive breast carcinomas. Multifocal tumors were excluded.

Results: Two hundred five N- cases were retrieved. Median size was 8 mm (range, 2 to 10 mm), 51 were T1a (25%), 152 tumors were T1b; 120 tumors (59 %) exhibited significant hormonal receptors (HR) expression. All patients had surgery, 65 % (n= 133) had a local irradiation. Ninety percent of HR+ patients (108/120) received hormonotherapy: 77 received aromatase inhibitors (AI) upfront or sequential; 23 received tamoxifen (TAM) alone 13 received LHRH agonists alone or in combination with TAM or AI. Forty-nine percent (n= 101) had chemotherapy (CT) (Anthracycline alone for 41 cases, taxane alone for 31 cases, sequential A/T for 28 cases and concurrent for 1 case), associated with TZM in 90 cases. TZM was administered without chemotherapy in 3 cases. Decision of adjuvant CT and/or TZM was associated with (all p<0.05) HR-negative status, Elston-Ellis grade 2/3 and high mitotic index (MI) while patients with HR+/ low MI tumors were rarely treated (p<0.01). With a 41 months median follow-up, there was a statistically significant difference in invasive recurrences between TZM treated patients and others (log-rank test p=0.04). Twelve of the 112 patients treated without TZM (11%) had a recurrent invasive disease including 6 metastatic cases and 3 fatal events. There was one invasive recurrence in TZM group. There were as much recurrences in T1a as in T1b tumors. Three of the 12 recurrences (25%) in the group without TZM occurred in T1a cases.

Conclusion: T1abN0M0 HER2 positive tumors have a significant risk of recurrence which could be avoided by adjuvant chemotherapy associated with TZM. Interestingly, there were no differences in the risk of recurrence between T1a and T1b. Adjuvant chemotherapy associated with TZM should not only be discussed in T1bN0 HER2−positive tumors but also in T1aN0 HER2−positive cases.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-18-03.
P2-19-04: Changes in Adjuvant Treatment of Early Breast Cancer in Italy between 2000 and 2008. The NEMESI Study Versus the NORA Study.
Authors: Mustacchi G , Cazzaniga ME , Pronzato P , Clavarezza M , Del Mastro L , Venturini M , Amadori D , Bidoli P , Boni C , Caruso M , Riccardi F , Dondi D
Published: June 2012

Background: In the early 2000s, we identified treatment patterns of early breast cancer (EBC) in Italy (NORA study). To ascertain whether attitudes have changed, we conducted a similar study in 2008. Patients and methods: In this retrospective study (NEMESI), we recorded the clinical, tumour and treatment characteristics of 1.894 EBC patients in 63 Italian oncological centres in 2008, and compared the results with those of NORA, on 3.515 patients in 70 same/similar Italian institutions, in 2000–2003. Tumor stage, surgery and endocrine-responsiveness are not comparable because of different recruitment protocols, patients charactheristics and adjuvant treatment strategies are perfectly comparable as a reliable picture of adjuvant strategies in Italy.

Results: There was no difference in age class distribution, menopausal status, ECOG performance status, tumor grade, ki67 and estrogen receptors content. HER2 status was simila but determined in 98% of cases in NEMESI vs 46.2% in NORA. The overall use of endocrine treatment (HT) increased from 80.3% in NORA to 83.5% in NEMESI (p = 0.005); the overall use of chemotherapy (CHT) decreased from 68.4% to 57.8% (p = 0.00001). HT alone increased from 31.6% to 42.2% (P = 0.00001) and CHT alone decreased from 18.8% to 16.2% (p = 0.017). The use of both treatments decreased from 49.2% to 41.6% (p = 0.00001). Trastuzumab was never given in NORA and in 15% of cases in NEMESI (85% of all HER2 positive cases).

The choice for HT was tamoxifen for 5 years in 32.5% of cases in NEMESI and 86.6% in NORA (p = 0.000001), and aromatase inhibitors for 5 years in 55.2% vs 13.3% of cases, respectively (P = 0.000001). The “switch” from tamoxifen 2–3 years to aromatase inhibitors 2–3 years was planned in 10.1% of cases in NEMESI and actually done in 12.9% of cases in NORA (p = 0.001). The overall use of LHRH analogues was significantly higher in NEMESI vs NORA (26.7% vs 3.0%, p = 0.00001). CMF-like regimens decreased from 37.0% in NORA to 9.1% (p = 0.000001). Anthracycline-containing regimens decreased from 52.1% in NORA to 48.8% in NEMESI; p = 0.0001) in favour of of regimens containing anthracyclines and taxanes, either in combination or sequential (0.9% in NORA vs 38.4% in NEMESIS, p = 0.000001). The use of taxanes alone regimens remained low (3.5% vs 3.7%, ns). The overall use of anthracyclines and taxanes increased from 53.0% to 87.5% and from 4.3% to 42.1%, respectively (both p =0.00001).

Conclusions: EBC treatment has changed significantly in 6 years. Adjuvant strategies are significantly different, with a great increase of aromatase inhibitors and LHRH analogues associated with tamoxifen; anthra-taxane combinations have also significantly increased.

Financial Support by Sanofi Aventis Italy

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-19-04.
P3-01-09: Oncogenic Activation of HSF1 Enables the Malignant Progression of Breast Carcinoma.
Authors: Mendillo ML , Santagata S , Koeva M , Fraenkel E , Ince TA , Whitesell L , Lindquist S
Published: June 2012

HSF1 is best known for its role as the master transcriptional regulator of the evolutionarily conserved heat-shock response. In mice, Hsf1 knock-outs dramatically reduce susceptibility to malignant transformation and tumor formation, and markedly increased survival in cancers driven by both oncogenic and tumor suppressor mutations. Likewise, RNAi-mediated knockdown markedly reduces the growth and survival of human cell lines established from cancers driven by a diversity of genetic lesions. The transcriptional network that HSF1 coordinates during heat-shock is known, but is unknown in malignancy. We compare HSF1 function in isogenic breast cancer cells of high and low malignant potential. HSF1 orchestrates a far-reaching transcriptional program that is dependent on transformation and the degree of malignancy. The oncogenic HSF1 program differs markedly from the classical heat-shock response. It is enriched for genes involved in a myriad of cellular processes known to be important in malignancy, including transcription, translation, glucose metabolism and cellular adhesion. It includes only a particular subset of heat-shock protein genes, and many of these are regulated in a manner that differs from their regulation by heat-shock. We also find that HSF1 is overexpressed and activated in a large subset of all conventionally defined classes of breast cancer. Moreover, tumors with high expression of the oncogenic HSF1 transcriptional network are strongly associated with poor outcome as monitored by metastasis and death. Our findings suggest that the oncogenic HSF1 activation program is rooted in fundamental aspects of tumor biology and will prove a powerful new tool in the clinical management of patients with breast cancer and, likely, other malignancies as well.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-01-09.
P3-01-12: Prognostic Impact of RANK, RANKL and OPG Gene Expression in ER Positive Primary Breast Cancer.
Authors: Ruckhaeberle E , Mueller V , Schmidt M , Saenger N , Hanker L , Gaetje R , Ahr A , Holtrich U , Karn T , Rody A , Kaufmann M
Published: June 2012

Background

The cell surface receptor RANK (receptor activator of NFκB), its ligand (RANKL) and the decoy receptor of RANKL osteoprotegerin (OPG) play an important functional role in bone physiology and in bone metastasis by regulating osteoclasts. Just recently it was shown that tumor-infiltrating lymphocytes can stimulate breast cancer metastases through RANK-RANKL signalling.

Material and methods: We analyzed gene expression of RANK, RANKL and OPG in a combined Affymetrix dataset of 307 ER positive breast cancers from our institutions which were either untreated of treated with chemotherapy. Kaplan Meier analysis of disease free survival and Cox regression analysis was applied to examine the prognostic value of the different markers.

Results: We observed no significant difference in survival when samples were analyzed according to either RANK or RANKL mRNA expression. In contrast when samples were stratified in quartiles of OPG expression a positive linear relationship of survival with the expression of OPG was observed. Moreover since OPG demonstrated a bimodal type of expression a cutoff value can be derived from the expression data. Using this cutoff value a hazard ration of 2.14 (95% CI 1.27−3.61; P=0.004 for low OPG expression was detected. OPG expression correlated with lower proportion of grade 3 tumors (15.7% vs 27%; P=0.022) and a higher proportion of PgR positive samples (86.2% vs 71.4%; P=0.002). No significant differences were observed for lymph node status, age, tumor size and HER2 status. In multivariate analysis only lymph node status remained significant while OPG, Ki67, age, grade, and PgR only displayed a trend towards significance.

Conclusion: Expression of osteoprotegerin seems to correlate with good prognosis in ER postive breast cancer. These data are in line with in vitro studies demonstration that OPG inhibits RANKL induced migration of tumor cells.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-01-12.
P3-02-01: A Novel Bispecific, Hexavalent, Antibody (HexAb) Inhibits Anchorage-Independent Growth and Reduces Invasiveness of Triple-Negative Breast Cancer Cell Lines In Vitro.
Authors: Goldenberg DM , Wang Y , Trisal P , Cardillo TM , Rossi EA , Chang C-H
Published: June 2012

Background

Combination therapy using two different monoclonal antibodies to achieve improved efficacy without increased toxicity is being pursued in various preclinical and clinical studies but, in principle, could be accomplished with a single bispecific antibody (bsAb). We note the elevated expression of the type-I insulin-like growth factor receptor (IGF-1R) and the trophoblast cell-surface marker (Trop-2) in diverse epithelial tumors, including breast cancers, and the increasing evidence of their correlation with poor survival. Therefore, we chose to explore the potential of 1R-(E1)-(E1), the bispecific HexAb constructed from hR1 (humanized anti-IGF-1R) and hRS7 (humanized anti-Trop-2) for treating breast cancers. Methods: 1R-(E1)-(E1) was generated by the Dock-and-Lock (DNL) method to comprise a full IgG of hR1 linked to two stabilized dimers of hRS7 Fab, and evaluated in three HER2−negative breast cancer cell lines: the non-evasive MCF-7, the moderately invasive MDA-MB-468, and the highly invasive MDA-MB-231. The in vitro characterizations of 1R-(E1)-(E1) included flow cytometry to determine cell binding, soft agar assay to evaluate the effect on anchorage-independent growth, and BD matrigel chambers to assess invasion properties. Statistical differences (P values) between two populations were determined by Student's t-test.

Results: All three cell lines were found to express both IGF-1R and Trop-2, with MCF-7 and MDA-MB-468 notably higher in IGF-1R and Trop-2, respectively. As expected, 1R-(E1)-(E1) bound to all three cell lines. At 50 μg/mL, 1R-(E1)-(E1) reduced the invasion of MDA-MB-468 to less than 10% of the untreated control, whereas under the same conditions, MDA-MB-231 appeared to be resistant, while the parental antibodies showed no effects. The ability of 1R-(E1)-(E1) to inhibit anchorage-independent growth was demonstrated at 200 nM in MDA-MB-231, with a statistically significant difference (P<0.041) when compared with samples treated with parental antibodies at the same concentrations. Cells treated with 1R-(E1)-(E1) produced few and much smaller colonies, the largest size of which was less than 1/10 of the untreated cells. The parental hR1 alone, but not hRS7, had some effect on inhibiting the growth of MDA-MB-231 in soft agar, presumably resulting from the down-regulation of IGF-1R.

Conclusions: These promising results warrant further evaluation of 1R-(E1)-(E1) in other breast cancer cell lines, as well as the exploration of new bispecific HexAbs that comprise different antibodies capable of targeting other solid cancers.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-02-01.