bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P5-10-22: Dose Dense Adjuvant Chemotherapy in Breast Cancer Patients with Five or More Nodes Involved: Results of a French Cohort with Long Term Follow-Up
Authors: Cuvier CC , Hocine FF , Hamy AS , Giacchetti SS , de Roquancourt AA , Charveriat PP , Marty MM , Lehmann-Che JJ , Porcher RR , Espie MM.
Published: April 2011

Introduction: Axillary node involvement remains the most important prognosis factor in breast cancer patients. In those with ≥ positive nodes, 5-year overall survival rates range from 47% to 22% and 5-year recurrence rate from 54% to 82%. Several trials have studied the impact of dose dense chemotherapy in node-positive breast cancer. Some have shown a significant improvement in relapse-free survival and even overall survival. However the power of these studies is often insufficient to conclude and the follow up is often short.

Objective: To provide safety and long term efficacy data of a dose dense chemotherapy regimen used in Saint Louis Hospital for patients with ≥5 positive nodes.

Materials and methods: Beetween 1990 and 2003, all patients with ≥5 positive nodes were treated with adjuvant dose dense chemotherapy: 6 cycles of epirubicin 75mg/m2, cyclophosphamide 1200mg/m2 q2w followed by 3 cycles of conventional chemotherapy. No prophylactic G-CSF was given.All patients received adjuvant radiation therapy. Of 95 patients with HR positive tumors,44 received adjuvant tamoxifene therapy after completion of chemotherapy. Patients were followed by clinical and laboratory examinations every 4 months for 3 years then every 6 months for 2 years and every year thereafter. A mammogram was performed each year.

Results: Patients characteristics:

Patients characteristics at inclusion. Figures are median (range) or no. (%).

(Her2 expression will be presented at the meeting.) Median time between surgery and chemotherapy was 30 days (9-91).Grade 3 or 4 toxicities were mainly: neutropenia (89%) gastro-intestinal toxicity(30%) febrile neutropenia 24% cardiac toxicity 2.6% toxic death:1 pt. Median follow-up since the initiation of chemotherapy:10.9 years. Median survival:11.3 years (95% CI 9.4-∞) and median disease-free survival 6.1 years (95% CI 4.6- 8).5, 10 and 15 overall survival rates were 76%, 56% and 41%respectively and disease-free survival were 54%, 37% and 34% respectively. Conclusion: In this very high risk selected population, our dose-dense chemotherapy regimen exhibits an exceptionnaly high 10-year survival rate. A sequential association with taxanes should be studied.

Figure available in online version.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-22.
Abstract P5-10-24: A Pragmatic Review of Adjuvant Chemotherapy Regimens in Early-Stage Breast Cancer — Hematologic Toxicities Experienced in a Single Institution
Authors: Tran M , Simmons CE , Haq R , Brezden CB.
Published: April 2011

Background: Chemotherapy-related toxicities are associated with substantial morbidity, mortality, and health care expenditures. Three newer common adjuvant chemotherapy regimens - 5-fluorouracil, epirubicin, cyclophosphamide plus docetaxel (FEC-D), docetaxel plus cyclophosphamide (TC), and docetaxel, carboplatin plus trastuzumab (TCH) - have emerged as promising therapies. The toxicities experienced with these chemotherapeutic regimens were reviewed in a clinical practice setting outside of clinical trial.

Patients and Methods: Patients (pts) with early-stage breast cancer treated with adjuvant chemotherapy (FEC-D; TC; TCH) at St. Michael's Hospital in Toronto, Canada, between August 2006 and May 2010 were identified. Charts were audited for the presence of neutropenia (defined asabsolute neutrophil count (ANC) < 1.0x109/L), use of granulocyte-colony stimulating factor (G-CSF), incidence of febrile neutropenia (FN; defined as a single oral temperature ≥38.3 0Celsius, or oral temperature ≥38.0 0C lasting over 1 hour, with an ANC < 1.0x109/L).

Results: Overall, 175 pts were reviewed in this study. The rate of neutropenia, FN, and use of primary prophylaxis with G-CSF are summarized in the table below for each regimen. Thirty pts on FEC-D (25.2%) experienced significant complications resulting in dose delay, dose reduction, and discontinuation of chemotherapy, as did 9.1% of pts on TC, and 27.3% of pts on TCH. There was one death associated with FEC-D while on G-CSF.

Conclusion: Our institution reports FN rates higher than originally reported in all three chemotherapy regimens with a greater hematologic toxicity profile with FEC-D. Further investigation with larger patient cohorts is warranted, to determine if there is a need for primary prophylaxis with G-CSF in patients receiving FEC-D, TC, and TCH.

Table 1: Outcomes associated with FEC-D, TC, and TCH chemotherapy regimens

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-24.
Abstract P5-11-08: Effects of Exemestane or Tamoxifen on Bone Health within the Tamoxifen Exemestane Adjuvant Multinational (TEAM) Trial: A Meta-Analysis
Authors: Hadji P , Asmar L , van Nes J , Menschik T , Hasenburg A , Kuck J , Nortier H , Jones S , van der Velde C , Ziller M.
Published: April 2011

Background: TEAM is the largest AI phase III trial comparing exemestane with tamoxifen followed by exemestane as adjuvant breast cancer therapy in postmenopausal women. We performed a meta-analysis of three randomized sub-studies of the TEAM trial conducted in Germany, the Netherlands/Belgium and the United States to determine the effects on bone health.

Methods: Patients were randomised to exemestane or tamoxifen as adjuvant therapy for hormone receptor-positive breast cancer. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry at baseline and after 6, 12 and 24 months’ treatment. Bone turnover markers were also measured.

Results: 412 patients were evaluable. Patients in the tamoxifen group showed a mean increase in lumbar spine BMD of 1.2% from baseline to month 12 and 0.2% to month 24. Patients in the exemestane group showed a mean decrease from baseline of 2.6% after 12 months and 3.5% after 24 months. There were significant differences in the changes in BMD at the lumbar spine between treatment groups (P<0.0001 at both timepoints). In the tamoxifen group, a mean increase in total hip BMD of 0.8% from baseline to month 12 and a mean decrease from baseline of 0.4% after 24 months was observed, compared with a mean decrease of 1.3% after 12 months and 3.3% after 24 months in the exemestane group. Changes in BMD from baseline at the total hip were also significantly different between exemestane and tamoxifen (P<0.05 at both timepoints). Bone turnover markers decreased from baseline with tamoxifen and increased with exemestane.

Conclusions: After 24 months, exemestane treatment resulted in decreases in BMD and increases in bone turnover markers. In contrast, BMD was increased and bone turnover markers were decreased with tamoxifen. BMD and bone turnover changes appeared to stabilise after initial treatment.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-11-08.
Abstract P5-11-11: Completion of 5-Years Adjuvant Endocrine Therapy in the Community
Authors: Makubate B , McCowan C , Dewar JA , Thompson AM.
Published: April 2011

Background: Adjuvant endocrine therapy is recommended by guidelines for all eligible patients with breast cancer for a minimum 5-year period. Shorter periods of treatment and low adherence to medication are associated with worse outcomes for patients. This study examined whether women in the community completed the full course of adjuvant endocrine therapy and whether they were adherent to their medication. Materials and Methods: A cohort of all women diagnosed and treated for breast cancer in the Tayside region of Scotland during the period January 1993 — December 2008 was identified. Information on dispensed prescribing was linked to hospital discharge records, breast cancer clinical audit, cancer registry and death certification for each individual patient. Patients were identified as starting either aromatase inhibitor or tamoxifen therapy with adherence and duration of use subsequently calculated from dispensed prescribing records. Results: 5,729 women were identified with an incident cancer within the study period. 71% were initially prescribed tamoxifen, 8% started aromatase inhibitors and 21% received no adjuvant endocrine therapy. 25% of women who started on aromatase inhibitors switched treatments, with 19% of those on tamoxifen switching. The majority of women had high adherence, the median figure was 91%, but 1,589 (35%) of women had adherence below 80% which was shown in previous work to increase the risk of mortality. For patients followed for at least 1 year, 51 (11%) started on AIs had stopped medication compared to 373 (9%) started on tamoxifen. At year 2, an additional 40 (12%) stopped AIs and 384 (11%) patients stopped tamoxifen. For 3 years follow up, an additional 39 (19%) stopped AIs, while 351 (11%) stopped tamoxifen. For patients followed for at least 4 and 5 years respectively, an additional 22 (26%) then 5 (20%) stopped AIs compared to 297 (11%) and 316 (16%) patients who stopped tamoxifen. Of the 3,613 patients with adequate follow up 1,876 (52%) stopped medication before completing a 5 year period. Conclusions: Half of all patients prescribed adjuvant endocrine therapy stop medication before completing the recommended 5-year period with approximately 20% stopping in the first two years. Over one in three patients have low adherence at a level known to increase the risk of mortality. All patients need to be encouraged to continue their treatment for the recommended 5-year period and to take it daily to ensure they receive maximum benefit from their medication.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-11-11.
Abstract P5-12-03: Concurrent vs. Sequential Administration of Adjuvant Trastuzumab in Early Stage Breast Cancer: A Systematic Review and Meta-Analysis
Authors: Lavasani SM , Mahinbakht A , Verma S.
Published: April 2011

Background: Overexpression/Amplification of the HER2 occurs in 15-18% of breast cancers. Adjuvant trastuzumab is now integrated in the care of most HER2-positive early stage breast cancers. However, an important question persists regarding the concurrent vs. sequential use of trastuzumab as adjuvant treatment in early stage breast cancer. A meta-analysis of randomized controlled trials (RCT) was undertaken to compare concurrent vs. sequential trastuzumab. The outcomes of interest were risk of recurrence, death and grade III and IV cardiac toxicity. Method: Systematic review of English literature retrieved from EMBASE (1980 to April 26, 2010), MEDLINE (1996 to April 26, 2010) and Cochrane database for the relevant studies. In addition, conference proceedings of ASCO and SABCS from 2004 to 2009 were searched for relevant abstracts. A manual search of the reference lists of the selected articles was performed in order to further identify relevant studies. The search strategy was conducted according to our well-defined inclusion and exclusion criteria. Our search strategy revealed 1262 citations. Only RCTs were included. The review was performed by 2 reviewers independently. The data analysis was conducted by Review Manager Version 5, which could not compare the number of recurrences and deaths head to head for concurrent vs. sequential trastuzumab. A Fixed effect model was used. When I square showed heterogeneity of >50%, sensitivity analysis was performed. Results: Six eligible trials were identified. Three RCTs used trastuzumab concurrently and 2 RCTs used trastuzumab sequentially. One RCT (NCCTG N9831) had 3 arms, chemo only control arm, sequential trastuzumab arm and concurrent trastuzumab arm. Pooled and sensitivity analysis of 4 RCTS comparing concurrent trastuzumab with chemotherapy showed total HR of 0.73 (P<0.00001) for reduction of recurrence and 0.78 (P=0.0006) for reducing the mortality. The pooled analysis of 3 RCTs comparing sequential trastuzumab with chemotherapy revealed total HR of 0.82 for reduction of recurrence (P<0.0001) and 0.93 for mortality (p=0.27). The cardiac toxicity in concurrent trastuzumab was in favour of control with risk ratio of 4.66 (P<0.00001) and in sequential treatment was also in favour of control with risk ratio of 9.90 (P<0.0001).

Conclusion: Concurrent trastuzumab with chemotherapy shows a greater improvement in DFS (HR: 0.73 vs. 0.82). HR for OS also favours concurrent trastuzumab (0.78 vs. 0.93). Cardiac toxicity in both concurrent and sequential trastuzumab favours control arms.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-12-03.
Abstract P5-14-08: The Impact of Immediate Breast Reconstruction on Surgical Complications and the Delivery of Adjuvant Chemotherapy
Authors: Chang R , Kirkpatrick K , De Boer RH , Mann GB.
Published: April 2011

Introduction: For women undergoing mastectomy immediate breast reconstruction (IBR) offers potential psychological benefits and increased quality of life. This study aimed to answer the question whether IBR might lead to higher complication rates and subsequently delay adjuvant chemotherapy (AdCT). Secondary aims included predictors for complications, and whether patients (pts) with worse tumour prognosis were less likely to undergo IBR.

Materials and Methods: Retrospective analysis was performed on 220 pts who underwent mastectomy ± IBR and received AdCT.

Results: Comparisons were made between the 107 pts who received IBR and 113 who had mastectomy alone (table 1). Women who were younger with less co-morbidity, lower BMI, and had better prognosis tumours were more likely to receive IBR. No statistically significant difference was found in the overall surgical wound complication rate between the groups. There was more return to surgery in the IBR group, resulting in a 9.8% (12/123) prosthesis loss rate. There was no significant difference in the average time to chemotherapy between the two groups. Conclusion: We found no evidence to suggest that IBR compromised the delivery of adjuvant chemotherapy, although there are significant risks of complications associated with reconstruction.

Table 1: Comparison between women who underwent mastectomy alone (no IBR) and women who

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-14-08.
Abstract P5-14-20: Clinical Features of Surgical Resection for Solitary Pulmonary Metastasis and the Discrepancy in Immunopathological Features between Primary and Metastatic Breast Cancer Lesions
Authors: Shien T , Nogami T , Doihara H , Nishimura R , Takabatake D , Masuda H , Ikeda H , Taira N , Ohsumi S.
Published: April 2011

Background: The treatment for metastatic breast cancer (MBC) is usually systemic therapy decided by the hormone and HER2 status of primary breast cancer lesion. There are some reports about the discrepancy in hormone and HER2 status between primary and metastatic lesion in these days. We have reported previously that the expression of ALDH-1 which considered the pathological markers of breast cancer stem cell in axillary lymph node matastases is a significant predictor of poor outcome in primary breast cancer patients (Figure 1). We evaluated the role of surgery in the diagnosis and treatment of a solitary pulmonary nodule (SPN) in breast cancer patients and demonstrated the significance of analyzing the immunopathological features in metastatic breast cancer lesion.

Methods: Between 1990 and 2006, 17 patients (PM) with SPN which were diagnosed breast cancer metastases underwent complete pulmonary resection and 36 MBC patients (AP) underwent autopsy after breast cancer related death in our hospitals. We retrospectively analyzed clinicopathological features and the expression of ER, HER2, Ki-67 and ALDH-1 in both primary and metastatic breast cancer lesions.

Results: The median age of PM patients was 53 (range 30-80). All PM patients had not other metastases and had undergone curative breast cancer operation. The pulmonary operation were partial pulmonary resection in 15(88%) and lobectomy in 2 (12%) patients. The median disease free survival (DFS) was 63 months (range 9-175). Median overall survival (OS) was 181 months and the median OS after pulmonary operation was 48 months. The median DFS and OS of AP patients were 21 and 43 months. All AP patients had multiple visceral metastases. We compared the immunohistlogical status between primary and metastatic lesion and evaluated the colletation with these status in metastatic lesion and prognosis in all patients. Conclusion: Pulmonary resection was effective to diagnose and the OS after resection was relatively long in PM patients. We report the value of the expression of ER, HER2, Ki67 and ALDH-1 in distant metastatic lesions.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-14-20.
Abstract P5-15-02: Characteristics and Prognosis of Patients Presenting with Isolated Axillary Nodal Metastases from Occult Breast Primary Carcinoma
Authors: Davidson JA , Tyldesley S , Speers C , Woods R , Chia S.
Published: April 2011

Background: Patients presenting with isolated axillary metastatic carcinoma represent a potentially curable subset of patients. As there are no published randomized trials, literature concerning this uncommon clinical entity is limited to small retrospective reports. These vary widely with respect to the information collected, span a large time period during which diagnostic and therapeutic options have advanced considerably, and are largely without a contemporary control group.

Methods: The British Columbia Breast Cancer Outcomes Unit (BCOU) database was searched to identify patients referred to the British Columbia Cancer Agency with a new diagnosis of isolated axillary metastatic cancer diagnosed between 2000 and 2005. Eligible patients were female, had pathological evidence of lymph node (LN) involvement but no evidence of a primary tumor or distant metastases on clinical workup. A series of control patients, with pathological T1 tumors and N1 involvement at presentation were selected from the BCOU database matched 3:1 for age, diagnosis year, tumor characteristics (histology, estrogen receptor status, HER2 status, and number of affected lymph nodes), and systemic treatment characteristics (adjuvant chemotherapy and/or endocrine therapy).

Results: 36 patients were identified to form the primary axillary cohort. The controls consisted of 1,406 patients, of whom 106 were matched for the above characteristics. Patients in the primary axillary cohort were fairly well-distributed among all diagnosis years, and all tumors exhibited ductal histology. 26 (72%) were estrogen receptor-positive and 8 (22%) were known to be HER2-positive. 9 (25%) patients underwent mastectomy. 33 (92%) patients received radiation therapy and 19 (53%) did not undergo any breast surgery. With a median follow-up of 5.2 and 5.4 years for the primary axillary cohort and the matched controls, the BCSS was 93% and 88% respectively. There were no locoregional recurrences documented in the primary axillary cohort.

Conclusions: This study represents one of the larger contemporary case control series of isolated axillary nodal presentations, demonstrating a good prognosis for this cohort of patients despite approximately half of the patients not having primary breast surgery.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-15-02.
Abstract P5-15-05: Applicability of Breast Cancer Guidelines and Knowledge Translation in a Community Oncology Setting
Authors: Han D , Hogeveen S , Trudeau-Tavara S , Buck J , Brezden-Masley C , Simmons C.
Published: April 2011

Background: The quality of a guideline may impact adherence to that guideline. Cancer Care Ontario (CCO) produces guidelines to help manage all stages of disease. CCO's staging and follow-up guideline suggests patients (pts) with stage I breast cancer require no further staging investigations, bone scan for stage II disease, and for stage III disease in addition to bone scan, chest and abdominal imaging. The guideline on bisphosphonate (BP) use in metastatic breast cancer pts indicates that all pts with bone metastases should be offered a BP. We assessed the efficacy of knowledge translation of these guidelines at a community oncology centre by correlating rate of adherence with the quality of the guideline as scored using the Appraisal of Guidelines for Research and Evaluation (AGREE) Instrument.

Methods: The quality of 2 breast cancer guidelines from CCO were assessed using the AGREE instrument. Two cohort studies of breast cancer pts seen were then conducted to evaluate the adherence to these guidelines. Specifically, staging investigations ordered on pts seen in our multidisciplinary clinic between January 2009 and April 2010 were recorded and correlated to pathological stage of disease. Our second cohort study reviewed breast cancer pts with bone metastases who died between 1999 and 2009, and initiation of a BP was recorded in order to determine adherence to the second guideline.

Results: Inadequate adherence was identified and correlated with low applicability scores for these two guidelines (58% and 33% respectively). Only 68 pts (61%) with bone metastases received BP for treatment between 1999 to 2009. 129 pts (56%) underwent unnecessary staging investigations.

Discussions: Non-chemotherapy breast cancer guidelines by CCO scored low in the field of applicability; this was confirmed by two retrospective cohort studies. Improvement in knowledge translation strategies are needed to improve adherence to practice guidelines set out by this national organization.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-15-05.
Abstract P6-01-03: Invasive Micropapillary Carcinoma (IMPC) of the Breast: An Uncommon but Aggressive Special Type of Breast Cancer
Authors: Acs G , Esposito NN , Kiluk J , Laronga C.
Published: April 2011

IMPC is an uncommon type of invasive breast cancer. However, in comparison to invasive ductal carcinoma of no special type (IDC), it is reported to have a more aggressive behavior. Our objective was to compare and contrast IMPC with IDC in terms of clinicopathologic features and outcome. One hundred-thirty-one IMPC cases were compared to 1295 IDC and 189 invasive lobular carcinoma (ILC). Medical records and pathology slides were reviewed for traditional factors (tumor grade, lymphatic invasion [LVI], lymph node [LN] status, stage, receptor status, treatment) and specific tumor features (extent of retraction artifact [RA]). Clinicopathologic features between groups were compared and clinical outcome of IMPC was recorded. All patients were women with a median age of 57.6 yrs (range 22-93) for IMPC, 56.3 yrs (range 22-96) for IDC and 60.7 (range35-85) for ILC, respectively (P<0.0001). There were no differences noted for family history, race, or presentation (symptomatic vs. screening). Surgical treatment was partial mastectomy in 770 (47.7%) and mastectomy in 845 (52.3%). All patients had axillary lymph node biopsy. The median tumor size was 2.2 (range 0.3-15.2) cm for IMPC, 2.0 (range 0.05-11.0) cm for ILC and 1.7 (range 0.05-19.0) cm for IDC, respectively (P<0.). The extent of micropapillary features in IMPC ranged from 3% to 100% with a median value of 20%. LVI was more likely to be present in IMPC (67.9%) compared to IDC (28.3%) and ILC (6.9%) (P<0.0001). Axillary LN metastases were seen in 71.8% of IMPC compared to 44.1 % of IDC and 54.5% of ILC (P<0.0001). IMPC and ILC was significantly more frequently ER and PR positive (P<0.0001 each) compared to IDC, while ILC was significantly less frequently HER2 positive (2.8%) compared to IDC (17.9%) and IMPC (8.2%). The mean percent of tumors showing retraction artifact (RA) was 60.2% in IMPC compared to 25.4% in IDC and 3.8% in ILC (P<0.0001). During a median follow-up of 24.3 months 19 (14.5%) and 17 (13.0%) IMPC patients developed local and distant recurrence, respectively. IMPC is an uncommon special type of invasive breast cancer but it is more aggressive in reference to IDC and ILC based on larger tumor size and more frequent the presence of LVI and LN metastases. The presence of IMPC features in breast cancers, even if present focally, should alert the clinician for the high likelihood of lymphatic tumor spread and an adverse biologic behavior.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-01-03.
Abstract P6-02-02: Evaluation of the Clinical Efficacy of Minimally Invasive Procedures for Breast Cancer Screening at a Teaching Hospital
Authors: Verenhitach BD , Elias S , Nazário AP , Patrocinio AC.
Published: April 2011

Objective: To assess the clinical accuracy of diagnostic procedures for breast cancer at a teaching hospital using internal auditing tools and quality control measures.

Study Design: Retrospective assessment of 500 patients who underwent core needle biopsy (wide-bore needle biopsy - WBN) of palpable or non-palpable breast nodes and also were submitted to at least one cytologic examination [fine needle aspiration cytology (FNA) and/or imprint of a WBN specimen]. For statistical assessment, we utilized the auditing tool and quality control proposed by the National Health Service — Breast Screening Program (NHSBSP).

Results: For FNA, specificity full (SPEC), positive predictive value (PPV), inadequate rates and suspicious rates were satisfactory while absolute sensitivity (AS), complete sensitivity (CS), false-negatives (FNs) and false-positives (FPs) were unsatisfactory. For imprint, AS, CS, inadequate rate from cancers and suspicious rate were satisfactory, and the remaining indicators were unsatisfactory. WBN displayed the best performance with AS, CS, FN, suspicious rate, SPEC and PPV, showing satisfactory results and only one unsatisfactory result (FP).

Comparison of quality control measures of fine-needle aspiration (n=395), imprint (n=182) and core-needle biopsy (n=500) performed at the UNIFESP-EPM Breast Clinic from January 2002 to April 2007 with the

Min — minimuml; Unif — Unifesp-EPM; PPV — Positive predictive value, NA — not applicable

Conclusion: Based on an overall analysis, WBN displayed the highest clinical efficacy compared with FNA and imprint and demonstrated adequate safety for confirming the appropriate diagnosis and management of patients, ensuring the efficacy of the service.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-02-02.
Abstract P6-03-01: High Percentage of Triple Negative Tumors Present as Palpable Masses
Authors: Kalu ON , Kurian A , Wapnir I.
Published: April 2011

Introduction: Approximately 15% of newly diagnosed breast cancers are triple negative tumors (TNT; ER-/PR-/HER2-), a subgroup with a particularly poor prognosis. This clinical-pathologic subtype corresponds to, but is not synonymous with basal-like tumors. These cancers are prevalent among African-Americans and BRCA mutation carriers. We hypothesize that TNT are more likely than other breast tumor subtypes to present as a palpable mass or appear between screening examinations. We compared the screening practices and detection modality of women with TNT at our institution.

Methods: Between December 2000 to February 2010, 346 women with TNT were identified through the Stanford University Cancer Center tumor registry. Medical records were retrospectively reviewed. Breast imaging screening was compared between women whose cancers presented as a palpable mass versus those which were detected on breast imaging. Patients without prior breast imaging, screening occurring >5 y prior to diagnosis or unknown imaging history were grouped together (UNK). 95% confidence intervals (CT)determined by modified Wald method.

Results: Mean age at diagnosis was 53y (range 25 to 97). 82 patients had BRCA mutation testing, of which 41 were positive. 58 women were < 40 y of age; 100 between 40-50 y; and 188 women > 50. 253 were detected on self exam. The rest were found on screening mammography (70), MR imaging (3), non-breast radiologic studies (9); unknown presentation (11).

54 cancers in women < 40 years of age were palpable. Of these, 7% (0.02- 0.18)had screening within 24m(onths), 6% (0.01-0.16)within 2 to 5y(ears) and 87% (0.75-0.94)were UNK. 74 women 40-50y of age with palpable presentations, 36%(0.26-0.48) had screening within 24m, 9%(0.04-0.19) within 2-5y and 54%(0.43-0.65)were UNK. 125 women >50 years of age with palpable presentations, 27%(0.21-0.36) had screening within 24m, 5% (0.02-0.10)within 2-5y and 67%(0.45-0.62) were UNK. Within this group 2 of 4 (<40), 23 of 27 (40-50), and 25 of 34 (>50) had detected masses within 12m of breast imaging. 30 patients carried BRCA mutations. 3 women <40 y had tumor detected on screening; 1 patient had screening at 15m, 2 were UNK. 22 in the 40-50y group were detected on screening; 41% (0.23-0.61)had screening within 24m, and 60%(0.39-0.77) were UNK. 48 women >50y had tumors detected on screening; 50% (0.36-0.64)had screening within 24m,8%(0.03-0.20)within 2-5y, and 42%(0.29-0.56) were ND. In this group, 5 of 9 (40-50), 16 of 24 (>50) had lesions detected within 12m of imaging. 8 patients with image detected tumor carried a BRCA-1 mutation. A total of 249 pts were of screening age and of those 95 were screened within 2 y; yet 65% of those presented with a palpable mass.

BREAST IMAGING PRIOR TO DIAGNOSIS, N(%)

Conclusion: Our data suggests that regardless of age, TNT present as palpable masses even among those undergoing breast screening.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-03-01.
Abstract P6-03-02: Breast Reduction Mammoplasty and Incidence of Occult Carcinoma. A 10 Year Experience
Authors: Mazhar K , Goyal A , Coulson S , Caddy C.
Published: April 2011

Background: The aim of this study was to report the incidence of cancer in reduction mammoplasty specimens and suggest alternative pragmatic cost-effective way of identifying and treating patients with carcinoma. Methods: All patients who underwent breast reduction surgery at Northern General Hospital over a 10-year period were identified from a prospective database. The histopathology reports and case records of all patients with significant abnormalities were analysed. All breast reduction specimens were sliced at 1 cm intervals and examined macroscopically. At least 3 blocks per breast were examined microscopically in addition to sampling of any grossly abnormal tissue.

Results: Between October 1999 and April 2010, 1,588 patients underwent reduction mammoplasty. The median age of patients was 38 years (range 16-75 years). Indications for surgery were macromastia in 1,194 (75.2%), congenital asymmetry in 182 (11.5%) and contralateral symmetry procedure post breast cancer surgery in 178 (11.2%). 9 specimens showed atypical hyperplasia (0.57%). 5 cancers were detected (0.31%). 4 of the 5 patients had normal mammograms 1-3 years before the reduction operation (not done in 1). Of these cancers, 4 were invasive (3 invasive lobular, 1 invasive ductal) (0.25%) (mean invasive tumour size 9 mm (SD 7.4)) and 1 was DCIS (4mm) (0.06%). A lump was felt macroscopically by the pathologist in 2 of the 4 patients with invasive cancer. The median age of patients with invasive cancer was 56 years (range 47-68 years). Patient found to have DCIS did not undergo further surgery while those with invasive disease underwent mastectomy (3) and axillary nodal staging (4). None of the patients with benign/normal post-reduction breast imaging had residual breast cancer on histology.

Conclusion: The incidence of occult carcinoma in reduction mammoplasty specimens is less than 0.5%. Pre-operative mammogram is not useful as 4 of the 5 patients with cancer had a normal mammogram 1-3 years before surgery and invasive lobular cancers are often not detected on mammogram. Mastectomy may be avoided in patients with no residual breast disease on post-reduction imaging.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-03-02.
Abstract P6-03-03: Could We Reduce the Number of Exams in the Follow-Up of Breast Cancer Survivors?
Authors: Tallet AV , Farnault BP , Moureau-Zabotto LV , Esterni BA , Salem N , Gonçalves A , Houvenaeghel GF , Jacquemier JD , Resbeut M.
Published: April 2011

Background. The aim of this retrospective study was to determine by which way was diagnosed any breast cancer recurrence after the end of the adjuvant treatment and to draw guidelines for exams for the follow-up. Materials and methods. Between January 1995 to December 2005, 5419 patients were treated for non metastatic breast cancer in our institute, out of which 662 experienced a relapse either local or metastatic. The charts of 608 of these patients were analysable, and retrospectively reviewed. For each case, we looked at the exams or clinical symptom which revealed the recurrence.

Results. Among the 608 patients who recurred, 173 patients (28%) experienced an isolated local relapse, while 12 experienced a contralateral breast cancer (2%), 423 experienced either a metastatic or metastatic plus local relapse (65% and 5%, respectively). Local relapses were detected in most of cases either clinically (42%) or on mammography and mammary ultrasound (US) (55%). An isolated increase of blood tumor marker (CA 15.3) revealed the relapse in 24% of cases (in 33% of cases for distant relapses and 3% for isolated local relapses). The remaining 67% of cases with metastases were diagnosed by clinical symptoms in 47% of cases, imaging in 22% of cases (bone scan in 6%, liver US 5%, mammography 1%, TDM 5%, chest X-ray 2%). In these cases of radiographically detected metastases clinical exam and/or tumor markers levels were abnormal in 42% of cases.

Conclusion. A follow-up with a systematically clinical exam, mammography and mammary US, and blood tumor markers assessment permits the diagnosis of 100 percent of local relapse, 100% of contralateral breast cancer, and 89% of metastatic disease. Thus imaging exams could be avoided routinely, with less stress for the patient and improvement of the health cost.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-03-03.
Abstract P6-03-04: Opening, Dynamic Prospective Cohort Research on the Small Focus Less than 1.1cm Shown by B Ultrasound in Breast
Authors: Fan Z , Shi A , Du H , Wu D , Fu T.
Published: April 2011

BACKGROUND: Ultrasound is the most frequent clinical way to examine breast in China. Because Chinese have small and high density breasts, mammography can not show some lesions, and it costs too much. There are 5%-10% patients detected small, nonpalpable lesions by ultrasound in clinic and physical examination. Most of the lesions are very small, without typical characteristics of malignant or benign tumor. So many positive results bother doctors and patients. OBJECTIVE To find an appropriate way to detect breast cancer early and reduce unnecessary biopsy. METHODS: A Opening, dynamic prospective cohort research on the small focus less than 1.1cm shown by B ultrasound has been performed from 1 st January 2009. 791 cases and 1064 lesions were selected to the study group. All patients are female, from 35 to 75 years old. The lesions are from 0.25 cm to 1.1cm in ultrasound and less than grade 3 in mammography according to BI-RADS. The patients are divided to 2 groups according to the mammography grade of BI-RADS. The first subgroup concludes 260 cases with grade 3, and the second subgroup concludes 531 cases with less than grade 2. The patients who were more than grade 4 in ultrasound according to BI-RADS accepted biopsy as soon as they got into group. Other patients accept ultrasound per 3 months and mammography per year. We will do biopsy when the lesions rise up to 130% of the original size, and when the lesion reduce to 70% of the original size in consecutive two times examination on ultrasound , the patient will leave the group. RESULTS: Total 70 cases were performed biopsy during 17months. 2 cases (0.7%) without family history of breast cancer were breast cancer during biopsy in the first subgroup.2 cases (0.3%) with family history of breast cancer were mastopathy with atypia during the procedure of follow up—biopsy in the second subgroup. CONCLUSIONS: Most small lesions which are negative on mammography are benign and need not be performed resection. Use of mammography can reduce unnecessary biopsy in Chinese. Ultrasound and family history of breast cancer should be considered well.

the cases of screening and biopsy

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-03-04.
Abstract P6-05-03: Analysis of College of American Pathologists Recommendations for Reporting HER2 Intra-Tumoral heterogeneity (ITH) on 1329 Breast Cancers
Authors: Allison KH , Dintzis SM , Schmidt RA.
Published: April 2011

Background: The College of American Pathologists (CAP) recently published recommendations for reporting intratumoral heterogeneity for HER2 gene amplification in breast cancers. These guidelines recommend reporting cases with between 5-50% of cells with HER2:CEP17 ratios

> 2.2 (or > 6 HER2 signals/cell) as “heterogeneous for HER2 gene amplification.” Because these recommendations lack biological and clinical foundation, we applied them to a large number of historical breast cancers and compared the ITH classification to routine FISH Her2 results. Materials and Methods: We collected Her2 and CEP17 counts in 32,116 tumor cells from 1329 consecutive breast cancer cases analyzed by FISH. Data from Excel counting sheets were imported to a SQL Server database for analysis and statistics; histograms and analyses were also performed in Excel. We specifically computed concordances between guidelines for traditional and intra-tumoral heterogeneity (ITH) reporting.

Results: 309 of 1,329 cases (23%) met the criteria for heterogeneous HER2 gene amplification by HER2:CEP17 ratio, but > 79% of these were non-amplified by standard FISH reporting criteria. Using Her2 signals per cell, ITH was found in 87 (6.5%) of cases and most of these were not amplified or equivocal by standard criteria.

Discussion: A significant proportion of breast cancers contain ITC heterogeneity based on CAP/ASCO reporting recommendations. The majority of these cases are non-amplified without consideration of ITH. Because it is not known whether these patients (who would not currently be treated) would benefit from HER2 targeted therapies, it may be premature to use the ITH reporting recommendations for clinical decision-making. More validation of ITH criteria and biological significance are needed.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-05-03.
Abstract P6-05-04: Quantification of Intra-Tumoral Heterogeneity for HER2 Gene Amplification by FISH with Proposed New (“High-ICR”) Reporting System
Authors: Schmidt RA , Dintzis SM , Allison KH.
Published: April 2011

Background: Current recommendations for reporting Her2 amplification by FISH have several problems, including imperfect concordance between different reporting methods, presence of an ‘equivocal’ category that is clinically problematic, and lack of accommodation for the common presence of intratumoral heterogeneity (ITH). Using a large dataset, we sought to better define ITH and develop a FISH reporting system that is more useful for patient management.

Materials and Methods: We analyzed HER2 and CEP17 counts in 32,116 individual tumor cells from 1329 consecutive breast cancer cases. Based on the individual tumor cell ratios (ICRs) and the overall average case ratios, cases were divided into three groups to explore the significance of ITH. These groups were as follows: 1) Uniformly non-amplified cases defined as < 5% of individual cells with a HER2:CEP17 ratio > 2.2 and an overall average case ratio < 1.8 (n=763). 2) Uniformly amplified cases defined as

> 90% of individual cells with a HER2:CEP17 ratio > 2.2 and the overall average case ratio > 2.2 (n=137). 3) Non-uniformly amplified defined as between 5-90% of cells with ratio > 2.2. (n=429). The Her2:CEP17 ratios for individual cells were then compared between groups to identify the ICRs characteristic of uniformly amplified cancers.

Results: ITH for HER2 gene amplification is very common and is present in non-amplified, equivocal and amplified cases by traditional reporting criteria. Cells with Her2:CEP17 ratios >= 4 are characteristic of uniformly amplified cases, are essentially absent in uniformly non-amplified cases and represent only 5.3% of cells in non-uniformly amplified cases (as defined above). Lower ratios are not characteristic of uniformly amplified cancers. Using an individual cell ratio >= 4 to define significantly amplified (“High-

ICR”) cells, the following diagnostic categories are proposed: uniformly amplified (defined as having >90% High-ICR cells), uniformly non-amplified (<10% High-ICR cells and heterogeneous with X% amplified cells (10-90% of High-ICR cells). The distribution of cases using this proposed reporting system versus the classic CAP/ASCO categories is shown in the below table.

Proposed ITH reporting system vs classic CAP/ASCO categories

Discussion: Intratumoral heterogeneity for HER2 gene amplification is common in amplified, non-amplified and equivocal cases by current reporting guidelines but not all heterogeneity is likely to be clinically significant. The High-ICR scoring system categorizes cases based on the number of cells with significant amplification, eliminates the problematic equivocal category. and directly reports the fraction of cells that are presumed to be most amenable to treatment. We propose that the High-ICR reporting system be further validated and adopted for clinical use.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-05-04.
Abstract P6-05-06: Clinical Presentation of Molecular Apocrine Subgroup of Breast Cancer: A Rather Aggressive Group of Tumor
Authors: Hamy AS , Leman S , Barritault M , Lehmann-Che J , Abuellelah H , Giacchetti S , Cuvier C , de Roquancourt A , Bertheau P , de The H , Marty M , Espie M.
Published: April 2011

Background: Estrogen receptor negative (ER-) breast cancer represents 30% of breast cancers. This heterogeneous group comprises at least the basal and HER2+ subgroups. Recent data, as well as our own, has observed that the HER2+ subtype is highly heterogeneous. Several teams have identified a new “apocrine” molecular subgroup of cancer, characterized by androgen receptor (AR) expresion in an ER-context. Here, we have retrospectively identified, based on a transcriptionnal signature, these apocrine molecular tumours and described their clinical presentation and evolution.

Material and Methods:

We retrospectively identified 60 patients treated in St Louis Hospital (Paris) from 1995 to 2008 and presenting the signature of the molecular apocrine subgroup (ERA-, AR+, FOXA1+) by Q-RT-PCR.

Results:

Mean age at diagnosis was 53,5 y.o. Tumours size were T2 or more in 78% cases. Histological types were ductal invasive with intraductal component (n=22), histological apocrine (n=3), and paget disease (n=4). Tumor grade was 3 in 68%, and 2 in 21%, with lymphovascular invasion in 37%. Excluding patients receiving neo-adjuvant chemotherapy, lymph node status was negative in 41%, and positive in 52% (1 to 3, 32%, more than 4N+, 20%). By immunohistochemistry 97.4% were PR-and 58.72% overexpressed HER2.

Surgery was conservative in 46%, and 48% patients underwent mastectomy. Sixteen patients received neoadjuvant chemotherapy (27%), 41 received adjuvant chemotherapy (68%), 16 received hormonal therapy (27%), and

16 received trastuzumab (27%). With a median follow up of 60 months, 34 events (local recurrence n=9, contralateral n=3, distant metastasis n=22), and 13 deaths occurred. Median disease free survival was 48 months.

Discussion:

In this cohort of apocrine molecular carcinomas, tumor phenotypes appears to be rather aggressive, with a high proportion of poor prognosis factors (grade SBR3, lymphovascular invasion, node involvement), and are generally well-correlated to a poor clinical outcome in this population that received heterogeneous treatments. Further data are needed to precisely characterise this particular breast cancer subtype, notably patients who are not eligible to Herceptin-based regimen.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-05-06.
Abstract P6-06-01: Relationship between Vitamin D Deficiency and Breast Cancer Histology: A Retrospective Database Review
Authors: Weinstock C , Zhu Y , Bao T , Buras RR , Hanna NN , Tkaczuk K , Chumsri S.
Published: April 2011

Background: Vitamin D deficiency has recently been shown to be correlated with high rates of developing breast cancer (Chen P et al, Breast Cancer Res Treat; Oct 2009). However, the association between the degree of vitamin D deficiency and specific histological subtypes of breast cancer remains unclear. Preclinical data has suggested that vitamin D plays an essential role in the terminal differentiation of breast cancer cells, and thus vitamin D deficiency would be associated with the pathogenesis of estrogen receptor negative tumors (Welsh J et al, Journal of Steroid Biochem Mol Biol; Feb 2003), in particular triple-negative tumors, which are associated with a particularly aggressive clinical course. Methods: Beginning in July 2008, the majority of newly diagnosed breast cancer patients at University of Maryland Greenebaum Cancer Center had Vitamin D 25-OH levels testedon initial presentation to the clinic. We conducted a retrospective chart review to obtain information about tumor histology and vitamin D levels in these patients. Results: We include data on 71 patients who presented with newly-diagnosed breast carcinoma or DCIS between June 2008 and December 2009. Average age at diagnosis was 57 (range 36-87), and 58% of patients were African American. Stage distribution of the cohort included; DCIS-3%, stage I-15%, stage II-41%, stage III-28%, and stage IV-10%. Overall, 80% of the patients were vitamin D deficient at diagnosis, with vitamin D levels under 30 ng/ml, and 57% had levels under 20 ng/ml. Patients with triple-negative tumors were the most likely to be vitamin D deficient at diagnosis (90%) compared to hormone receptor-positive patients (75%), and they had the lowest mean and median vitamin D levels compared to all other patients.

Percentage of patients with Vitamin D deficiency

Vitamin D level by histological subtype

Hormone receptor-positive patients were significantly more likely to have normal vitamin D levels at diagnosis and significantly less likely to have severe deficiency (level <10 ng/ml) than those with hormone receptor-negative tumors (p=0.037). African-American women in this cohort were also more likely to be severely vitamin D deficient, with levels <10 ng/ml, than were Caucasian women (34% vs. 7%, p=0.048). Conclusion: Vitamin D deficiency is common among patients with newly-diagnosed breast cancer. Patients with triple-negative tumors may have a higher likelihood of being vitamin D deficient than patients with other histological subtypes.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-06-01.