bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P2-10-25: Prognostic value of relative change in tumor marker CA 27.29 in early stage breast cancer – The SUCCESS trial
Authors: Hepp P , Tesch H , Forstbauer H , Rezai M , Beck T , Schrader I , Kleine-Tebbe A , Hucke J , Finas D , Soeling U , Zahm D-M , Weiss E , Beckmann MW , Janni W , Rack B
Published: August 2014

Background: MUC1 based tumor markers like CA27.29 (TM) in breast cancer are routinely used in metastatic disease as early marker for treatment efficacy. However, in early stage disease data is sparse. In this analysis, we looked at the impact of individual change in CA27.29 on prognosis instead of using a threshold.

Methods: The SUCCESS Trial compares FEC-docetaxel (Doc) vs. FEC-Doc-Gemcitabine (Doc-G) regime and two vs. five year treatment with Zoledronat in 3754 patients (pts) with primary breast cancer (N+ or high risk N0). We measured CA27.29 after surgery but before chemotherapy (CHT) as baseline and compared it to CA27.29 levels 2 years thereafter with the ST AIA-PACK Ca27.29 reagent using MUC-1 for AIA-600II (Tosoh Bioscience, Tessenderlo, Belgium).

Results: CA27.29 data is available of 2,015 pts. 119 pts (5.9%) had TM over the threshold of 32U/ml before CHT and 56 (2.8%) 2years thereafter. To examine the relative change of tumor marker, pts were divided into 3 groups:

increase: change >=5 U/ml; stable: change <±5U/ml; decrease: change > = −5 U/ml.

123 (6.1%) pts had increasing (>=5 U/ml), 1419 (70.4%) had stable, 473 (23.5%) had decreasing TM levels from before CHT to 2 years thereafter. The majority of pts with increasing TM (86 pts; 69.9%) had levels below the usual threshold of 32U/ml at all times. Patients with an increase >=5 U/ml had an 81% increased risk for recurrence (HR = 1.810 [CI: 1.111–2.948]) and reduced overall survival (HR = 1.020 [CI: 1.004–1.037]). In the multivariate analysis taking into account tumor size, nodal status, grading, age, hormonal and HER2/neu receptor status increasing CA27.29 levels were an independent prognostic marker.

Conclusions: An increase of the tumor marker CA27.29 2 years after CHT compared to pre-chemotherapy baseline was associated with a worse prognosis. By using this approach, more patients at risk for recurrence were detected than with the standard threshold approach. Therefore, the use of relative change could help to identify more patients at risk for relapse who might benefit from an intensified follow up.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-25.
Abstract P2-10-35: The grade of accompanying DCIS in IDC as important prognostic factor
Authors: Kim JY , Moon H-G , Han WS , Noh DY
Published: August 2014

Backgrounds: The issue of whether concomitant ductal carcinoma in situ (DCIS) affects the prognosis of with invasive breast cancer is important but studies of this have reported inconsistent results. So we aimed to assess the character and prognostic difference in infiltrating ductal carcinoma (IDC) according to accompanying DCIS status.

Methods: We reviewed the medical records of the patients who underwent surgery for IDC. Male patients, patients who had received neoadjuvant chemotherapy, patients with synchronous bilateral breast cancer, follow-up periods <6months or those with other malignancies were excluded from the study. In cases in which a DCIS component was present in IDC, the degree of differentiation and the presence of necrosis were assessed to subdivide DCIS into two groups; low and high grade.

Results: A total of 1751 patients were included, and 1384 patients (79.0%) had concomitant DCIS; 337 had low-grade DCIS, and 1047 patients had high-grade DCIS. The low-grade DCIS group had a significantly lower TNM stage than the high-grade DCIS group. The majority of cases with low-grade DCIS, were ER-positive (85.2%), PR-positive (81.3%) and had low Her-2 (98.7%).

When we analyzed the survival rates according to the presence of DCIS, no statistical significance was founded. However, a subgroup analysis showed that the patients with low-grade DCIS survived significantly longer than other patients, whereas those with high-grade DCIS had poorer survival (5 year event-free survival rate; low-grade DCIS vs. without DCIS vs. high-grade DCIS, 97% vs. 93% vs. 86%, p = 0.001). Specially, in patients with lymph node involvement, accompanying high-grade DCIS was independent predictor distant metastasis (HR 5.0, p = 0.026, 95% CI 1.21–20.92).

Conclusion: The important factor that affect prognosis of IDC with DCIS is not the presence itself of DCIS component but the grade of DCIS. The patients with low-grade DCIS had a good prognosis and those with high-grade DCIS had a poor prognosis.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-35.
Abstract P2-11-15: Development of a web-based survey tool to assess change in breast cancer (BrCa) survivor knowledge after receipt of cancer treatment summary and survivorship care plan (SCP).
Authors: Custer JL , Rocque GB , Wisinski KB , Jones NR , Donohue S , Koehn TM , Champeny TL , Terhaar AR , Chen KB , Peck KA , Tun MT , Wiegmann DA , Sesto ME , Tevaarwerk AJ
Published: August 2014

Intro: The Institute of Medicine advocates survivorship care plans (SCPs) as tools to improve coordination of care by improving survivor knowledge of follow-up recommendations and future risks. No evidence exists to demonstrate that SCPs impact survivor knowledge of diagnosis, treatment, or future/chronic side effects. Furthermore, there is a lack of information on existing surveys and their ability to assess survivor knowledge regarding these issues, without change over time. The purpose of this research is to report on the development of a survey assessing knowledge of diagnosis, treatment, and side effects in BrCa survivors.

Methods: Using existing literature, two oncologists created 24 questions addressing knowledge of diagnosis, treatment, and side effects. Content experts including breast oncology providers (representing multiple subspecialties), Survey Research Shared Service (SRSS) and patient advocates reviewed and revised the questions. Next, potential questions were administered in a group setting to BrCa survivors to evaluate clarity of instructions and survey wording. The Breast Cancer Knowledge (BreaCK) survey was further revised based on survivor feedback.

For pilot testing, BrCa survivors were recruited from clinic to test BreaCK survey content and clarity. Survey 1 was administered in clinic online. SRSS conducted verbal assessments regarding content after Survey 1. Four weeks later, survivors received Survey 2 via email and answered online. Correct answers were abstracted from the medical record.

Results: Nine subjects completed both surveys. Qualitatively, little intra-subject variation was seen between surveys. Subjects did not feel that the survey was burdensome or intrusive. No subject was able to correctly answer all questions. Final survey adjustments were made based on subject feedback and common incorrect answers encountered when grading the surveys. Specifically, subjects had difficulty understanding “endocrine or hormone therapy.” Furthermore, subjects reported guessing in response to some questions – additional answer categories were added, including “I don't know.”

Conclusion: Survivor knowledge did not change significantly between surveys. This suggests survivor knowledge was not impacted by the survey over the four-week interval. The revised BreaCK survey may be a useful tool for assessing survivor knowledge of diagnosis, treatment and side effects. A larger cohort of BrCa survivors is being recruited, starting Summer 2012, and will be evaluated using the survey.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-15.
Abstract P2-12-01: Prospective Evaluation of Joint Symptoms in Postmenopausal Women Initiating Aromatase Inhibitors for Early Stage Breast Cancer
Authors: Crew KD , Chehayeb Makarem D , Awad D , Kalinsky K , Maurer M , Kranwinkel G , Brafman L , Fuentes D , Hershman DL
Published: August 2014

Background: Aromatase inhibitors (AIs) are widely prescribed to postmenopausal women for the adjuvant treatment of hormone-sensitive breast cancer (BC). However, musculoskeletal complaints can lead to nonadherence and early discontinuation. The aim of this study was to characterize the natural history of the AI-induced arthralgia syndrome and determine predictors of worsening symptoms.

Methods: Postmenopausal women with stage I-III BC initiating adjuvant AI therapy were enrolled. All patients completed the following questionnaires at baseline and every 3 months for a year: Modified Brief Pain Inventory-Short Form (BPI-SF), Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and the Modified Assessment of Chronic Rheumatoid Affections of the Hands (M-SACRAH). Higher scores reflect worse symptoms. Quality of life was assessed using the Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES). Hand grip strength was measured at each visit with a Martin dynamometer. Paired t-tests were performed to compare follow-up evaluations to baseline. Linear Regression was performed to evaluate the association between baseline symptoms and change in symptoms.

Results: A total of 169 patients have been consented, 3-month data is available on 102; 6-month data on 85. Median age: 63 (42–89); White/Black/Asian/Hispanic: 61.48/30.33/3.28/25.6; median BMI (kg/m2): 28 (12–50). Compared to baseline, there was a statistically significant increase in BPI pain severity and endocrine related symptoms on the FACT-ES at 3 and 6 months. Significant changes in the BPI pain interference, M-SACRAH pain and stiffness, WOMAC function, physical well-being on the FACT-ES, trial outcome index and pinch grip strength were seen at 3 months; however these changes did not remain significant at 6 months. Logistic regression models evaluating predictors of patient reported outcome measures and grip strength were performed. Baseline score was the strongest predictor of worsening symptoms (p < 0.01) after correcting for age, prior chemotherapy and baseline joint conditions.

Conclusions: Treatment with adjuvant AI therapy is associated with significant worsening of joint pain and stiffness which is most prominent at the 3 months evaluation. Patients with baseline joint symptoms are at greatest risk for worsening symptoms on AIs.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-12-01.
Abstract P2-12-10: Psycho-spiritual therapy for improving the quality of life and spiritual well-being of women with breast cancer
Authors: Loghmani A , Jafari N , Zamani A , Farajzadegan Z , Bahrami F , Emami H
Published: August 2014

Objective: Psychological distress and morbidity are common consequences of diagnosis and treatment of breast cancer and associated with poor quality of life (QOL). Among several approaches, spirituality has been shown to be significantly associated with improving the quality of life of these patients. The aim of this study was to assess the role of psycho-spiritual therapy intervention in improving the quality of life and spiritual well-being of patients with breast cancer.

Methods: This was a randomized controlled trial study which was conducted in the Breast Cancer Research Center, St. S. Al-Shohada hospital, Isfahan, Iran. Sixty-eight patients with breast cancer were randomized to either psycho-spiritual therapy intervention group or control group who received routine management and educational programs. Before and after 6 weeks of psycho-spiritual therapy sessions, the quality of life was evaluated using Cancer quality-of-life questionnaire (QLQ-C30) and its supplementary breast cancer questionnaire (QLQ-BR23) and Spiritual well-being was measured using the Functional Assessment of Chronic Illness Therapy Spiritual Well-being scale (FACIT-Sp12). Multivariate, repeated-measures ANOVA, T-test and Paired T-test were used for analysis using Predictive Analytic Soft Ware (PASW, version 18) for windows.

Results: In all sixty five patients actually completed the six-week intervention and were evaluated for the outcomes. The mean Global health status score/QOL reached from 44.37 (SD: 13.03) to 68.63 (SD: 10.86), (p < 0.001), (Cohen's d effect size: 2.16, 95% CI: 1.56–2.78). There was a statistically significant difference in all functional scales of QLQ-C30 (p < 0.05) as well as spiritual well-being after intervention. (p = 0.02)

Conclusions: The results of this trial showed that the psycho-spiritual therapy program can improve the spiritual well-being and QOL of women with breast cancer. This program, with its ease of implementation and home practice, could be adopted in comprehensive care programs for women with breast cancer.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-12-10.
Abstract P2-13-10: Prospective randomized and multicentric evaluation of cognition in menopausal breast cancer patients receiving adjuvant hormonotherapy: a phase III study (Preliminary results)
Authors: Vanlemmens L , Delbeuck X , Servent V , Mailliez A , Vanlemmens L , Lefeuvre-Plesse C , Kerbrat P , Petit T , Fournier C , Vendel Y , Clisant S , Bonneterre J , Pasquier F , Le Rhun E
Published: August 2014

Background: Cognitive impairment has been considered to be a possible adverse effect of aromatase inhibitors (AI). The aim of the study was to compare the impact of tamoxifen or AI on verbal memory (Rey auditory-verbal learning test) and other cognitive functions (memory, executive and attentional functions) after 6 months of treatment.

Methods: In this randomized, open-label phase III study, menopausal patients treated with adjuvant hormonotherapy for early breast cancer were enrolled at the end of the radiotherapy. Patients over 70 years, with a history of cognitive disorder or with prior chemotherapy were excluded. Detailed neuropsychological assessments and quality of life evaluations were performed before the 1st administration of hormonotherapy and then 6 months later. Considering the usual norms of the auditivo-verbal Rey test, an alpha risk of 5% and a 95% power, 27 patients per arm had to be included. Statistical analyses included Chi2 test and Student tests when appropriate.

Results: 62 consecutive evaluable patients were randomized in 2 arms between March 2009 and April 2011. Patients received tamoxifen in arm A (n = 31) and AI in arm B (letrozole n=17; anastrozole n=12; exemestane n= 2). Median age at inclusion was 61.4 years. The median time since menopause was 10 years. Characteristics of the breast tumor and initial neuropsychological evaluations did not differ significantly between the 2 arms. After 6 months, we observed a significant decline of the performance at the episodic memory test (immediate recall of the Rey auditory verbal learning test) (p = 0.0015) in arm A only and a significant improvement on executive measures (Trail Making Test and Stroop test) (respectively p = 0.03/p = 0.002) in arm B. Quality of life didn't differ after 6 months of treatment.

Conclusions: These preliminary results do not support that AI have a worse adverse effect on cognitive functions than tamoxifen after 6 months of treatment. A confirmation is planned after one year of treatment.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-13-10.
Abstract P2-14-01: Fulvestrant vs exemestane for treatment of metastatic breast cancer in patients with acquired resistance to non-steroidal aromatase inhibitors – a meta-analysis of EFECT and SoFEA (CRUKE/03/021 & CRUK/09/007)
Authors: Johnston SRD , Chia S , Kilburn LS , Gradishar WJ , Cameron D , Dodwell D , Ellis P , Howell A , Im Y-H , Coombes G , Piccart M , Dowsett M , Bliss J ,   the SoFEA and EFECT Investigators
Published: August 2014

Background: Optimal endocrine treatment (trt) for post-menopausal women with ER+ advanced breast cancer (ABC) progressing on or following a non-steroidal (NS) aromatase inhibitor (AI) is unclear. The EFECT study showed no difference in efficacy between the steroidal antiestrogen fulvestrant (F) & steroidal AI exemestane (E) in this setting (HR = 0.96, 95%CI: 0.82, 1.13; p = 0.65). Pre-clinical data suggest F may be more effective in a low estrogen environment. SoFEA investigated F combined with anastrozole (F+A) in patients (pts) with acquired resistance to previous AI compared with F alone & F alone vs. E. The combination of F+A was no better than F (HR = 1.00, 95%CI: 0.83, 1.21; p = 0.98) nor F alone better than E (HR = 0.95, 95%CI: 0.79, 1.14; p = 0.56); the lack of added benefit for F+A is consistent with previous 1st-line studies that have assessed this combination versus A alone (FACT & SWOG-S0226).

Methods: SoFEA is a multi-center partially blinded randomized phase III study postmenopausal women were allocated to F plus A (F+A n=243), F plus placebo (n = 231) or E (n = 249). Similarly, EFECT is a randomized, double-blind, placebo controlled, multi-center phase III trial of F (n = 351) versus E (n = 342) in postmenopausal women (see table). However, given the differences in prior endocrine therapy/responsiveness within SoFEA & EFECT populations, an individual pt meta-analysis combining data from SoFEA & EFECT will be conducted enabling exploration of putative effects within specific pt subgroups to establish evidence in support, or not, of a pt subgroup sensitive to F at the dose used in these trials. Subgroups to be analysed include receptor status, visceral involvement, AI sensitivity, age, NSAI setting & time on NSAI.

Results: 723 pts (480 in F & E) were enrolled from 82 UK & 4 South Korean centers (03/2004-04/2010) in SoFEA. 693 pts were enrolled from 138 centers worldwide (08/2003-11/2005) in EFECT. Trt was well tolerated in both trials; serious adverse events were rare. The meta-analysis will be conducted in July 2012 & results presented.

Conclusion: Combining individual pt data from SoFEA & EFECT via meta-analysis will provide definitive clinical information on pt's response to F at the dose used in these studies, in particular whether certain pts with acquired resistance to NSAI do experience benefit of use of this antiestrogen as opposed to E.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-14-01.
Abstract P2-14-03: “Ethinylestradiol” is beneficial for postmenopausal advanced breast cancer patients heavily pre-treated with endocrine agents
Authors: Iwase H , Yamamoto Y , Murakami K-I , Yamamoto-Ibusuki M , Tomita S , Omoto Y
Published: August 2014

Purpose and Methods: Estrogen deprivation therapy using aromatase inhibitors is a standard therapy in postmenopausal hormone-dependent breast cancer. Paradoxically, low-dose estradiol was reported to be beneficial for the postmenopausal patients who have been heavily pre-treated with long-term sequential anti-estrogen therapies. To determine efficacy and safety of ethinylestradiol (3mg/day oral), a phase 2 study has been performed for the postmenopausal patients with advanced or recurrent breast cancer who became resistant to sequential endocrine treatments. The primary endpoint was clinical benefit rate, secondary were safety, objective response rate and time to progression. The interim data will be reported because of the extremely beneficial results.

Results: Eighteen cases with ER-positive tumor which showed resistance to previous sequential-endocrine therapies including SERMs and/or aromatase inhibitors were registered from Oct 2010 to May 2012. Their mean age was 62 years-old and the mean observation time was 9.2 months. Nine cases were evaluated as partial response, 1 case as long NC, 3 cases as stable disease, and another 2 cases as progressive disease. In three cases of all 18 cases, the estradiol administration was withdrawn within 1 week with their early endocrine-related symptoms, such as nausea, general fatigue and fever. Duration of effect in the case of the PR (including the 4 ongoing cases) was more than 24 weeks. All of 9 responders had high ER expression in the primary or metastatic tumor and had a history of long-term endocrine therapies in metastatic setting and had response to previous endocrine therapies. Serum estradiol levels elevated as 30–100pg/mL, and FSH was suppressed below premenopausal levels in 4 weeks later administration. Although the weight gain, irregular vaginal bleeding, or endometrial thickening was observed in patients treated with long-term treatment, there was no severe adverse event, such as deep venous thrombosis or other malignancies in this series.

Discussion: The mechanism of low-dose estrogen treatment can be considered the estrogen-induced apoptosis. The high ER expression and the response to previous endocrine therapies might be recognized as predictive factor of this treatment. This low-dose estrogen therapy may contribute to overturn the common sense of the endocrine therapy for breast cancer.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-14-03.
Abstract P2-16-01: Prospective breast cancer quality evaluation application developed for native Android tablet and web browser for improving mutltidisciplinary breast cancer care
Authors: Grobmyer SR , Raum N , Sposato V
Published: August 2014

Introduction: Easy to implement, prospective and user-friendly data collection tools are needed to insure optimal breast cancer care as defined by national quality measures. Prospective quality measurement can effectively allow rapid identification of gaps in care and identification for sources of programmatic improvement in multidisciplinary care.

Methods: Our group has designed a novel prospective quality assessment tool system, which consists of 3 major integrated components: 1) a web application for administration and reporting of the data, 2) a native Android tablet application for real-time data collection of breast cancer quality parameters during tumor board, and 3) a backend database where parameters are stored and reported on.

Results: The web application is the primary interface for the breast cancer coordinator (BCC) to enter information for the applicable Tumorboards. Quality parameters for measurement as determined by the breast program leadership are entered into the system by the BCC on the web application. The BCC will also enter medical record numbers of patients to be presented at each tumor board in the web based system. In order to maximize work flow and reduce error, the system was designed to interface with the hospital electronic medical record for retrieval of patient demographic data based on medical record number entry.

The Android tablet is the interface to the system during weekly breast cancer tumor board. The tablet application facilitates real time, prospective collection of: tumor board attendance, tumor staging, tumor type, and collection of center chosen and required breast cancer quality measures. Data collected on the android system is stored in real time a central and secure database.

Real time quality data analysis and graphical display for user defined time periods is available on the web application and Android tablet. Required tumor hospital tumor registry data is also compiled in real time reports to faciliate communication with the hospital tumor registry.

Conclusions: A novel real time Android based solution has been developed for real time breast cancer care quality and tumor registry information. Use of this technology greatly simplifies data collection required for participation national breast cancer accreditation organizations such as NAPBC as well as the American Joint Commission on Cancer. Its ease of implementation and use favor its widespread adoption. Efforts to quantify the impact of this unique tool on quality of performance in a multidisciplinary breast cancer program are underway.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-16-01.
Abstract P3-01-02: Correlation of Mammographic breast density and tumor characteristics in Korean breast cancer patients
Authors: Cho JY , Ahn SH , Lee JW , Yu JH , Koh BS , Kim HJ , Lee JW , Son BH , Gong G-y , Kim HH
Published: August 2014

Introduction: Western studies have demonstrated high breast density as a strong risk factor for breast cancer, it is poorly understood whether breast density affects the diverse phenotypes of breast cancer. We examined the association between various tumor characteristics and mammographic breast density in women with breast cancer.

Methods: We conducted a cross-sectional analysis in 910 Korean women diagnosed with breast cancer to evaluate the associations between breast density and tumor size, lymph node status, lymphovascular invasion, histologic grade, estrogen receptor, progesterone receptor, HER2. Breast density was classified as fatty (percent density less than 50% by a computer-assisted thresholding program, named “Cumulus™”; n = 470) or dense (percent density 50% or more; n = 440) for the cancer-free breast at the time of operation. Logistic regression was used to examine whether the relationships were modified by adjustment for body mass index, age at diagnosis, age at first birth, menopausal status, history of breast-feeding, and breast cancer staging.

Results: Total 910 patients were involved, the mean age and median age at the operation was 48 years old (range 20–82), and the mean percent density was 48.09 (SD = 9.62 %: normally distributed, Kolmogorov-Smirnov test p = 0.32). Crude analysis shows that tumor size over than 0.5cm were more likely to have dense breasts compared with women with a tumor size <=0.5 cm (OR = 3.21, 95% CI = 1.59–6.45, p = 0.001 for tumor sizes 0.6–1.0cm; OR = 2.02, 95% CI = 1.09–3.74, p = 0.03 for tumor sizes 1.1–1.5cm; OR = 1.8, 95% CI = 0.97–3.33, p = 0.06 for tumor sizes 1.6–2.0cm; and OR = 1.64, 95% CI = 0.92–2.94, p = 0.1 for tumor sizes 2.1cm or more). PD and histologic grade shows reverse association between histologic grade 1 and grade 2,3. Progesteron receptor positive patients tend to have more dense(OR = 1.27, 95% CI=0.97–1.66, p = 0.07) breast than receptor negative patients, although after adjustment of age the statistical significant disappeared. Percent density was not significantly associated with, ER (p = 0.74), HER2 (p = 0.72).

Conclusion: These results suggest that breast density is associated with tumor size and histologic grade and progesterone receptor positivity. Additional studies are needed to address whether these associations are due to just density masking the detection of some tumors, biological causation, or both.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-01-02.
Abstract P3-01-03: Breast density profile in a prospective large breast cancer screening program in South Brazil.
Authors: Caleffi M , Zignani J , Clarissa A , Ademar BJ , Ribeiro R , Dakir DF
Published: August 2014

Introduction: Women involved in breast cancer (BC) screening of NMPOA cohort, in South Brazil, are undergoing their 8th year of follow up. As mammography breast density is a well-established risk factor for breast cancer, since the beginning of this study, all mammograms were characterized according to breast density Birads pattern. Recently, a study published in the JNCI showed an association of this pattern of breast density with tumors that presented more aggressive characteristics.

Objective: To characterize the mammography density patterns of women involved in a prospective NMPOA cohort, and describe the mammography density appearance of those diagnosed with BC, correlating it with genomic classification and stages.

Methods: First screening mammogram of all women in the cohort was reviewed. All mammograms were classified according to BIRADS® patterns of density, which take into account the percentage of fibroglandular tissue (A: less than 25%; B: from 25 to 50%; C: from 50% to 75%, and D: more the 75%). Also, we compared breast density among the 17 incidental breast cancers diagnosed during follow up. Genomic classification and staging of the diagnosed cancers was described.

Results: A total of 2943 first mammograms were done until the end of women accrued inclusion in the cohort (April of 2006). Women's age ranged from 40 to 69 years. From these, 820 were A density, 893 B, 970 C and 260 D (graphic 1). Until November 2011, 17 cancer cases were found in the screening population. From these, 04 were A, 06 were B, 06 were C and 1 were D (graphic 2).

Cancer staging and genomic classification according to each mammogram density are summarized on Tables 1 and 2. No differences were observed in BC staging when we compared the A and B density with C and D (p = 1.0). The same occurred with the genomic classification (p = 0.48).

Conclusion: Our screening population has a predominance of low mammogram densities, probably due to the high body mass index observed in previous studies of this cohort. With respect to cancer cases, the absence of statistical significance results suggests that longer follow up will be necessary for definitive conclusions.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-01-03.
Abstract P3-01-04: Surgical management of mammographic microcalcification is improved by full field digital mammography (FFDM)
Authors: Bundred SM , Zhou J , Hurley E , Wilson M , Morris J , Bundred NJ
Published: August 2014

Background: Preoperative diagnosis of impalpable breast lesions correlates closely with the number of surgical procedures required for treatment. Correct diagnosis of mammographic microcalcification as DCIS or invasive cancer is important because lesions upgraded to malignant diagnosis at surgery require repeat surgical procedures in 44% of cases (BASO Audit 2011).

Methods: To determine the impact of FFDM (FFDM only since April 2010) on diagnostic accuracy, positive predictive value (PPV) and surgical management of MM. Screening and symptomatic women with mammographic microcalcification (n = 1125) in one visit were reviewed. Demographic information; pre and post operative diagnosis and number of surgical procedures were recorded for pre FFDM (8/ 2007 to 3/2010: n=710) and post FFDM (4/2010 to 5/2011: n=413).

Results: Overall 299 (106 invasive) and 144 (62 invasive) malignant lesions were diagnosed before and after FFDM introduction.

Reduction in PPV of biopsy for mammographic microcalcification was observed (SFM PPV 42.6%: FFDM PPV 34.6% (p < 0.01)). Upgrade of B3/4 lesions reduced (SFM 50% (21/42) vs. FFDM 21.7% (5/23): p < 0.05) and pre-operative diagnosis of DCIS improved (88.6% vs. 94%) using digital mammography.

Correct histological pre-operative diagnosis permitted a single therapeutic operation for 76.7%, compared to 66% of mammographic microcalcification where pre-operative diagnosis was inaccurate (p < 0.001).

Re-excision rates for DCIS lesions >20mm fell from 34.1% (60/176) to 21.1% (19/90) with FFDM (p <0.05).

Conclusions: Correct pre-operative diagnosis of mammographic microcalcification using FFDM has reduced second therapeutic procedures for mammographic microcalcification, decreased upgrade of B3/4 lesions at diagnostic surgery, but increased benign non-operative biopsies for mammographic microcalcification.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-01-04.
Abstract P3-02-01: Mammographic Screening: Good Prognosis Tumor Biology in Screen-detected Breast Cancers
Authors: Drukker CA , Schmidt MK , Rutgers EJT , Cardoso F , Kerlikowske K , Esserman LJ , Slaets L , Bogaerts J , van't Veer LJ
Published: August 2014

Introduction After the introduction of population-based screening breast cancer incidence increased while breast cancer mortality declined. Our previous analyses suggested screen detection might be associated with a higher likelihood of a biologically low risk or even ultralow risk tumor assessed by the 70-gene signature (MammaPrint™). (Ultralow 70-gene signature defined as indexscore > 0.6, no distant metastasis observed at 5 years in the original 78 patients with no adjuvant systemic treatment.) The aim of this study is to determine the proportion of biologically low and ultralow risk tumors among the screen-detected tumors. Second, to evaluate the impact of analog versus the more sensitive digital screening technique on the biology of tumors detected.

Methods All Dutch breast cancer patients enrolled in the MINDACT trial (EORTC-10041) accrued 2007–2011, who were invited for the Dutch screening program (biennial, age 50–75), were included (n = 1381). The proportions of 70-gene signature high, low and ultralow risk were calculated for patients with screen detected (n = 694), interval (n = 366), and symptomatic, non-screening (n = 321) carcinomas, taking into account analog vs. digital technology. Co-variants, such as age, tumor size, histological type, ER, progesterone receptor (PgR) and HER2/neu-oncoprotein (ERBB2) will be included in a multinominal logistic regression model to assess both confounding and effect modification by technology type; these data are pending and will be available during SABCS 2012.

Results Among the screen-detected tumors, 33% had a high risk 70-gene signature tumor and 67% had a low risk tumor (table 1). A significant difference was seen between the screen-detected carcinomas and interval carcinomas (p X2 test = 0.001) in all 70-gene signature risk groups. Among the screen detected carcinomas, 41.5% was detected using analog mammography and 58.5% was detected using digital mammography. Analog mammography detected 26.4% high risk, 31.9% low risk and 41.7% ultralow risk tumors. This is significantly different using digital mammography (p X2 test = 0.001), which detected 37.7% high risk, 32.8% low risk and 29.6% ultralow risk tumors.

Conclusion Screen detection was found to be associated with a higher likelihood of a biologically low risk tumor. Half of all screen-detected low risk tumors had an index score above 0.6, indicating an ultralow risk of distant metastasis. The transition from analog to digital mammography resulted in a decrease in detection of ultralow risk tumors and an increase in the detection of high risk tumors. Screen-detected low risk biology tumors are frequent and comprehension may aid to minimize overtreatment.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-02-01.
Abstract P3-02-14: INTEGRATED PROGRAM FOR BREAST CANCER CONTROL: PARTIAL PRESENTATION OF THE RESULTS OBTAINED INTHE FIRST 24MONTHS OF OPERATION
Authors: Blanco EC , Borges MM , Pinotti M , Gennari MB , Ribeiro IM , Nascimento CCP , Santos LFG , Sahium RC
Published: August 2014

Introduction Breast cancer is a public health problem in Brazil. This is due to the difficulty of primary prevention (eliminating risk factors or to diagnose and treat precursor lesions), with a consequent increase in the incidence and mortality from this cancer. The current challenge arises from the lack of access to a few specialized centers, which in turn ar e not always qualified for diagnosis and prompt treatment.

Objective To develop a strategic plan aimed at two management priorities: resolubility diagnostic and fast treatment of women with clinical or secondary changes to mammographic screening.

Methodology The Oswaldo Cruz Alemão Hospital (OCAH) in partnership with the Ministry of Health of Brazil has developed and deployed in the region of the Mooca - City of St. Paul the Integrated Program for Breast Cancer Control (IPBCC), which begins in the primary prevention (health education and removal of factors risk), continues with the mammographic detection and early diagnosis, modern instrumental in a Center for Diagnostic Detection and Tracking (CDDT), and culminates in the surgical and radiotherapy, ad juvant chemotherapy and hormone therapy or not, according to a standardized protocol. The care is coordinated in single query by mastologists trained in resolving service, with the participation of radiologists, oncologists, social workers, psychologists, nutritionists and health educators.

Results From January 2010 to December 2011 were met 12266 women, mean age 58 years (range, 22–89) of which 100 were diagnosed with breast cancer and the proportion of carcinomas was of 8 per 1000. The detection rate mammography, ultrasound, and by both methods were: 0.30, 0.30 and 0.25, respectively. Forty-one percent of cancers corresponded to stages Tis N0M0 (3%) and T1N0M0 (38%) predominantly in women aged less than 50 years (38% of the sample). The average time between diagnosis and recorded start of surger y or chemotherapy was 42 days (range 19–68). As for quality of care, satisfaction was 99% (n = 12143).

Conclusions The experience in resolving service provided a significant increase in the number of initial cases showing detection ratesper image consistent with the age distribution of population. It is expected that the tracking time and quality of service, allow the prevalent cancers cease to be diagnosed, privileging the incidents. The median time to diagnosis and early treatment of patients with cancer was significantly lower the average of 120 days recorded in some public reference services.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-02-14.
Abstract P3-03-01: 3D mapping of total choline in human breast cancer using high-speed MR spectroscopic imaging at 3T: initial experience during neoadjuvant therapy
Authors: Posse S , Zhang T , Royce M , Dayao Z , Lopez S , Sillerud L , Casey L , Eberhardt S , Lomo L , Rajput A , Russell J , Lee S-j , Bolan P
Published: August 2014

OBJECTIVE: To assess the feasibility of quantitative high-speed MR spectroscopic imaging (MRSI) of total Choline (tCho) as an adjunct to dynamic-contrast enhanced MRI to improve lesion characterization and monitor treatment response in patients undergoing neoadjuvant chemotherapy (NAC).

METHODS: Twelve patients with infiltrating ductal carcinoma (Table 1) were studied using a clinical 3T MR scanner (Siemens, Erlangen, Germany) equipped with 8- and 16-channel breast array (Hologic Inc., Bedford, MA). Four patients were studied before NAC. Four patients were studied once during NAC. Two patients were studied before and within 2–7 days of treatment initiation. One of these patients participated in an additional scan after 5 months of treatment. Two additional patients were studied at 3 time points during NAC. Measurements were performed using PRESS prelocalized 3D Proton-Echo-Planar-Spectroscopic-Imaging (PEPSI) using TR/TE=2000ms/135ms, matrix size up to 32×16×8, voxel size = 1cc, and total acquisition time of 10 minutes (including water reference scan). Additional data were collected at TE 60 ms to enhance sensitivity for detecting tCho and J-coupled resonances. TE-averaging (8 steps, DTE: 2.5 ms) was employed to minimize gradient sideband artifacts. Quantification of tCho in reference to tissue water was performed using spectral fitting and relaxation correction.

RESULTS: Strongly elevated tCho with maximum concentration up to 5.3 mmol/kg was measured in 9 patients with enhancing lesions larger than 2 cc volume (Table 2). Decreases in tCho were measured in all four patients who were followed during neoadjuvant chemotherapy. Decreases in tCho were measurable during the first week of neoadjuvant treatment in responders, consistent with previous studies. Our preliminary data also indicate that the combination of concentration and spatial extent of detectable tCho may be the most sensitive marker of treatment response.

CONCLUSION: This study demonstrates feasibility of quantitatively mapping tCho in invasive breast carcinoma using high-speed MRSI. The long-term goals are to utilize high-speed MRSI as an early predictor of treatment failure in women undergoing neoadjuvant therapy (i.e. chemotherapy, endocrine therapy or biologic therapy) for breast cancer and to develop an improved screening protocol for high-risk patients.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-03-01.
Abstract P3-03-03: A tri-modality imaging assessment algorithm to evaluate neoadjuvant therapy response in patients with operable breast cancer
Authors: Umphrey H , Bernreuter W , Bland K , Carpenter J , Falkson C , Forero A , Keene K , Krontiras H , Meredith R , Urist M , De Los Santos J
Published: August 2014

Background: To determine the negative predictive value (NPV), positive predictive value (PPV), accuracy, sensitivity and specificity of a pre-surgical tri-modality imaging assessment algorithm to determine complete pathologic response (pCR) post neoadjuvant therapy in patients with operable breast cancer.

Methods: A retrospective analysis was performed on data collected from patients receiving neoadjuvant therapy and pre-surgical breast magnetic resonance imaging (MRI), ultrasound (US) and mammography between 2004 and 2010 at our institution. Tri-modality imaging was reviewed by a single blinded breast radiologist and evaluated for predetermined modality specific parameters as defined in Table 1. The NPV, PPV, accuracy, sensitivity, and specificity were calculated on the basis of the final surgical pathology report with a complete pathologic response in the breast defined as no residual invasive disease or in situ disease.

Results. Eighty-three tumors in 83 patients with a mean age of 50 (range 27–70) were evaluated. Twenty-three patients had a pCR. The NPV, PPV, sensitivity, specificity, and accuracy of tri-modality imaging algorithm for pCR were 0.87, 0.95, 0.95, 0.87 and 0.93 utilizing a cut-point of ≤ 5 for complete response by imaging. The mean score for patients with pCR was 4.61 (range 3–10) with 3 patients scoring above 5. The mean score for patients with residual disease was 7.73 (range 5–11).

Conclusions: A tri-modality imaging scoring algorithm is predictive of complete pathologic response. This algorithm will be tested in a developing prospective trial that will also assess the additive value of tumor bed biopsy in patients who achieve a score of 5 or less.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-03-03.
Abstract P3-04-01: Protein pathway activation mapping of the I-SPY 1 biopsy specimens identifies new network focused drug targets for patients with triple negative tumors
Authors: Wulfkuhle JD , Wolf D , Gallagher RI , Yau C , Calvert V , Espina V , Illi J , Wu Q , Boe M , Yan Y ,   I-SPY TRIAL-1 Investigators, Liotta LA , van't Veer L , Esserman L , Petricoin EF
Published: August 2014

Background: Identification of new therapies and predictive biomarkers is needed for patients with triple negative (TN) breast cancer. Elucidating pathway activation in cancer is critical as these proteins represent targets for many of the new molecular therapeutics and companion diagnostic markers. The I-SPY TRIAL (CALGB 150007/150012, ACRIN 6657) is a trial of neoadjuvant anthracycline- and taxane-based chemotherapy that provides longitudinal biopsy specimens and molecular and clinical/pathological characterization.

Methods: Tumor epithelium was procured by Laser Capture Microdissection from 149 pretreatment frozen biopsy specimens (T1) and 102 frozen biopsy specimens collected 1–4 days after first chemotherapy treatment (T2). Reverse Phase Protein Microarray was used to measure the activation of 39 and 100 signaling proteins in the T1 and T2 biopsies, respectively, including drug targets for Phase I-III and FDA cleared therapeutics. Associations between pathway activation and response to chemotherapy (RCB 0/1 vs. 2/3) and relapse-free survival (RFS) were evaluated for the triple-negative (TN) patient population at each time point and for changes between T1 and T2. Significance thresholds for response and RFS were as follows: Wilcoxon rank sum test p < 0.05; Cox proportional hazard model, likelihood ratio p < 0.05.

Results: We focused our analysis on protein changes in patients who had poor clinical outcomes (Table 1)

We observed systemic activation of receptor tyrosine kinases such as MET and ALK in the T2 biopsies from patients that recurred, and VEGFR activation was seen in the T1 relapsed tumors. Activation in the AURORA-PLK1 cell cycle signaling network was seen with increased activation in the T2 biopsy from patients who did not respond to therapy and had poor RFS. Dynamic changes in ERK activation were revealed with decreased ERK activation between T1 and T2 time points associated with recurrence.

Conclusions: Our analysis has revealed activation and increased expression of proteins involved in proliferation (Ki67), DNA repair (phosphorylated p53) and protein kinases in patients with TN disease who had poor clinical response. These events, if validated, point to potential treatment options that could be considered for non-responding TN breast cancer patients. VEGFR, ALK and MET, have FDA cleared therapeutics that could be rationally proposed for rapid clinical investigation, and there are numerous investigational agents that target AURORA and PLK1 in the clinic. Further validation is required to explore the significance of these ongoing findings with the hope that the analysis could lead to molecularly rationalized therapies for patients with TN tumors.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-04-01.
Abstract P3-04-05: Kinomic and phospho-proteomic analysis of breast cancer stem-like cells
Authors: Leth-Larsen R , Christensen AG , Ehmsen S , Moeller M , Palmisano G , Larsen MR , Ditzel HJ
Published: August 2014

Cancer stem cells are thought to be responsible for tumorigenic potential and to possess resistance mechanisms against chemotherapy- and radiation-induced cancer cell death, while the bulk of a tumor lacks these capacities. The resistance mechanisms may cause these cells to survive and become the source of later tumor recurrence, highlighting the need for therapeutic strategies that specifically target pathways central to these cancer stem cells. The CD44hi/CD24−/low compartment of human breast cancer is enriched in tumor-initiating cells; however the functional heterogeneity within this subpopulation remains poorly defined.

From a triple-negative breast cancer cell line we isolated and cloned CD44hi single-cells that exhibited functional heterogeneity according to cancer stem cell features, such as tumor formation in immunodeficient mice, mammosphere formation, invasion and migration abilities and sensitivity to chemotherapeutics.

Quantitative proteomic analysis of these clones revealed several proteins, including kinases, exhibiting altered expression levels, while other proteins exhibited altered phosphorylation levels. The quantitative proteomic approach was based on post digestion dimethyl labeling followed by TiO2 enrichment of phosphopeptides. Moreover, analysis of the flowthrough fraction revealed quantitative changes in the total proteome. Transcriptomic analysis using Affymetrix Human Gene 1.0 ST Arrays revealed similar alterations at the gene expression level.

We used these single cell clones to further investigate the molecular mechanisms underlying the association between selected proteins, some of them phosphorylated, and cancer stem cell features. Furthermore, phosphosite-expression was investigated with NetworKIN that predicts in vivo kinase-substrate relationships.

Our studies reveal pathways that are regulated by protein phosphorylation and include relevant kinase targets for drug discovery. Our results support functional heterogeneity in the breast cancer cell compartment and hold promise for further refinements of prognostic marker profiling of cells with cancer stem cell-like features.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-04-05.