bluuebunny/crossref_metadata_2025 huggingface dataset:
P3-07-01: Are the Findings of ASOCOG Z0011 Applicable to District General Hospital Breast Unit – And How Should They Change Our Practice?
Authors: Olsen SB , Amr B , Omar A , Smith J , Thomson S , Monib S , Lai LM
Published: June 2012

Background: There has been considerable debate on the management of the axilla in breast cancer patients with lymph node metastasis found on sentinel lymph node biopsy (SLNB) following publication of the ACOSOG Z0011 study. This study conclude that axillary lymph node dissection (ALND) does not add any benefit to overall and disease free survival in some patients with positive SLNB. However it is not know if the patient characteristics of this study are transferable to other settings. A previous UK study has suggested that only a minority of patients from an academic specialist centre fit the ASOCOG Z0011 criteria and that the patient populations may not be comparable. The aim of our study was to assess the applicability of the Z0011 study to our patient population of a large District General Hospital in the UK and to what extent it should influence our practice.

Methods: The Z0011 eligibility criteria for inclusion in analysis were applied to all patients undergoing SLNB for invasive cancer at West Hertfordshire Breast Unit from 2007–2011. These were: no neo-adjuvant chemotherapy, clinical T1 and T2 tumours, breast conserving surgery followed by whole breast radiotherapy and 1–3 positive nodes on SLNB. Patent characteristics and results were compared using fisher's exact test.

Results: In our unit a total of 434 patients underwent SNLB of whom 64(14.7%) met the inclusion criteria of Z0011. Our patient population was comparable to that of Z0011 with regards to lymphovascular invasion, proportion of patients with micro-metastases and those with additional lymph nodes found on completion ALND. Our patients had significantly more T2 tumours. The only other statistically significant difference was in the proportion of estrogen receptor(ER) and progestrogen receptor (PR) positivity.

Conclusion: Only a small proportion (14%) of patients undergoing SNLB in our patient population fit the criteria for Z0011. This was a higher proportion than in the previous UK study of this type. Similar to this study we found the proportion of patients with T2 tumours were greater in our patient population compared to Z0011. This is most likely a reflection of this unit not being a screening centre and brings in to question the international generalisability of Z0011. However the only other significant difference in our patients was a lower risk profile in terms of hormone rector positivity with more ER/PR positive and fewer ER/PR negative patients. The implications of Z0011, will in our practice, not make a significant difference to the rate of ANLD. We are however considering changing our patient management based on the result of Z0011 and this current study of our population, to offer no further axillary surgery to patients over 50 with T1 and ER/PR positive tumours who otherwise fit the Z0011 protocol.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-01.
P3-07-11: Multicenter Comparative Study between One-Step Nucleic Acid Amplification (OSNA) Whole Node Assay and Standard Frozen Section Histology: Intraoperative Molecular Assay for Sentinel Lymph Node Metastases in Early Breast Cancer Can Avoid a Second Surgery.
Authors: Espinosa-Bravo M , Ramos T , Aizpurua Gomez M , Sao Avilés A , Peg Carmara V , Sancho M , Gónzalez-Orus JM , Xercavins Montosa J , Ramos M , Rubio IT
Published: June 2012

Studies on intraoperative assessment of sentinel nodes by frozen section in breast cancer have reported low sensitivity rates. Recently, a molecular-based procedure to detect lymph node metastases, one-step nucleic acid amplification (OSNA) assay, has been developed. OSNA assay can assess a whole lymph node and yields definitive semi quantitative results. The aim of this study was to evaluate the ability of intraoperative assessment comparing sentinel lymph node (SLN) metastases with OSNA assay versus routine H&E frozen section (FS) histology.

METHODS: A cohort of 478 consecutive patients diagnosed in 2010 with early breast cancer in two centers was analyzed. Frozen section was performed intraoperatively in 228 patients and OSNA assay in 250 patients. Patient characteristics were evaluated in both groups and rates of metastasis detected by both methods were compared.

RESULTS: Patients and tumor characteristic are summarized in the table.

A median of 1,95 SLNs were assessed by FS and a median of 2,06 SLNs by OSNA (p=0.15). Intraoperative histopathological assessment detected 67 SLNs metastasis by FS and 107 SLNs metastasis by OSNA assay (p=0.07). There were no differences in rates of macrometastasis (54 by FS and 74 by OSNA) and micrometastasis (13 by FS and 33 by OSNA) (p=0.09). When compared the OSNA assay with permanent section, 92 SLNs had metastasis by permanent section (63 macrometastasis and 29 micrometastasis) with no statistically significant differences (p=0.5).

SLNs metastasis were found in 71 patients (31,1 %) by permanent section and in 83 (33,2 %) by OSNA assay (p=0.69).

Axillary lymph node dissection (ALND) for metastatic SLN was performed in 148 patients, 79 (31,6 %) in OSNA group and 69 (30,2 %) in the permanent section group (p=0.68). All patients diagnosed by OSNA had a complete ALND during the initial surgical procedure. On the other hand, ALND was performed in 51 patients (73,9 %) in the permanent section in the initial surgery, and ALND was performed in a second surgical procedure in18 patients (26 %), due to false negative results of the FS (p<0.001).

CONCLUSIONS: The OSNA assay can detect SLN metastasis as accurately as conventional pathology, with no increased detection of positive SLNs. Given the definitive pathology of the SLN intraoperatively, the use of OSNA can reduce the need for a second surgery in 26 % of patients with breast cancer and a positive SLN.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-11.
P3-07-13: Validation and Comparison of Models To Predict Nonsentinel Lymph Node Metastasis in Chinese Breast Cancer Patients with Positive Sentinel Lymph Nodes.
Authors: Chen K , Jia W , Zeng Y , Fan M , Su F , Li S
Published: June 2012

Background: Several models for predicting the risk of nonsentinel lymph node (NSLN) metastasis in breast cancer patients with positive sentinel lymph nodes (SLNs) have been developed. Independent validation of these models in different populations is necessary before clinical application. This study aimed to validate and compare these models in Chinese patients.

Patients and Methods: A total of 159 breast cancer patients with positive SLNs treated at our institution were included. Chi-squared tests, RP-ROC, CART and multivariate logistic regression were used to analyze the risk factors for NSLN involvement in our population. ROC curves, calibration plots and false-negative (FN) rates were evaluated for 11 reported models. The threshold of each model for classifying patients into the low-risk group was adjusted to render the FN rate close to 10%.

Results: In total, 81 (50.9%) patients had at least one NSLN involvement. Univariate and multivariate analyses revealed that the number of negative SLNs (P<0.01, HR=0.63) and the metastasis size of the positive SLNs (P<0.01, HR=1.15) independently predicted the NSLN status in our population. The Cambridge and Mou models outperformed the others, both with AUCs of 0.73. The other models performed as follows: the Mayo, Tenon, MDA, MSKCC, Ljubljana, SNUH and Louisville models had AUCs of 0.68, 0.66, 0.66, 0.64, 0.62, 0.61 and 0.60, respectively. The Stanford and Saidi models did not present any discriminative capabilities, with AUCs of 0.54 and 0.50, respectively. The Cambridge, MSKCC and Mayo models were well calibrated. The Ljubljana model did not calibrate well.

With adjusted thresholds, the Mayo model outperformed the others by classifying the highest proportion of patients (20%) into the low-risk group. The Cambridge, Mou and MDA models defined 17.0%, 14.5% and 15.1% of patients as low-risk, respectively.

Conclusion: The Cambridge and Mou models performed well in Chinese patients. ROC curves, calibration plots and FN rates should be used together for the accurate evaluation of prediction models. The analysis of the clinicopathological features of the targeted population is critical for the selection of the most appropriate model. The models specifically designed for patients with micrometastases or macrometastases of SLNs are needed in the future.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-13.
P3-07-15: Sequential Peri-Areolar and Peri-Tumoural SPECT/CT Lymphoscintigraphy Has Identified High Rates of Discordance in Both Axillary and Internal Mammary Sentinel Lymph Node Mapping.
Authors: Noushi F , Spillane A , Gebski V , Snook K , Gillet D , Cooper R , Allwright S , Uren R
Published: June 2012

Introduction: The release of the MA20 intergroup trial results has confirmed the importance of locoregional radiation on local and distant disease control and survival. Sentinel lymph node (SLN) evaluation is the gold standard for regional lymph node evaluation and radiation oncologists continue to utilize the nodal staging to plan adjuvant locoregional therapy. Despite over a decade of experience in SLN evaluation there persists a common belief that the lymphatic drainage of the whole breast is to anteropectoral axillary lymph nodes. Several different lymphoscintigraphy injection techniques are in use with claims that they all identify the same axillary sentinel nodes. However this is not based on a high level of evidence. The evolution of SPECT/CT has led to the accurate anatomic identification of SLN, hence the different lymphoscintigraphy techniques can now be directly compared.

Method: 38 patients underwent double sequential lymphoscintigraphy (peri-areolar followed by peri-tumoural) separated by 1–7 days. Patients were referred by 4 surgeons to 3 separate lymphoscintigraphy centres with standardisation of tracer substance (99mTc-antimony sulfide colloid), lymphoscintigraphy and SPECT/CT evaluation techniques. The degree of discordance in sentinel node evaluation was defined as:

Type 1 - One study demonstrates SLN(s) in a nodal basin [axilla or internal mammary chain (IMC)] and the other study demonstrates none. Type 2 - Both studies identified SLN(s) in a nodal basin however the SLN(s) are all different. Type 3 - Both studies identified SLNs in a nodal basin, however some SLN(s) are identical and others not.

Results:

Notably 21 patients (55%) had either axilla or IMC lymphoscintigraphy discordance. Two patients had both axilla and IMC lymphoscintigraphy discordance.

The majority of discordance was identified in the IMC. In the concordant IMC lymphoscintigraphies neither study demonstrated IMC SLN. There were no studies that identified identical IMC nodes in both PA and PT lymphoscintigraphy.

Discordant axillary drainage was more evident in patients with lateral sector tumours compared to IM discordance with medial sector tumours.

Conclusions: Accurate lymphoscintigraphy is the road map to assist a surgeon identify lymph node metastases. In turn accurate staging will determine appropriate adjuvant therapy decisions particularly regional node irradiation. This study demonstrates a high degree of discordance between PA and PT lymphoscintigraphy techniques in 55% of patients. Inadequate lymphoscintigraphy can result in unrealized false negative results, which could impact patient outcomes and clinical trial results.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-15.
P3-07-27: ROCK II Expression Can Be a Potential Marker of Non-Sentinel Lymph Node Metastasis in Breast Cancer Patients with Sentinel Lymph Node Involvement.
Authors: Shigematsu H , Taguchi K , Shiotani S , Kawaguchi H , Nishiyama K , Ohno S , Okada M
Published: June 2012

(Background) It becomes controversy whether axillary lymph node dissection is mandatory performed for breast cancer patients with positive sentinel lymph nodes (SNs), given that more than half of patients with a positive sentinel lymph biopsy have no metastasis in non-sentinel lymph nodes (non-SNs). Rho-associated kinase (ROCK) is essential part in tumor invasion and metastasis, and its activation is reported to be potential marker of lymph node metastasis.

(Purpose) The purpose of this study was to evaluate the expression of ROCK II as predictive factor of non-SNs metastasis in breast cancer patients with positive SNs.

(Patients and Method) ROCK II protein expression was determined using immunohistochemical analysis on formalin-fixed and paraffin-embedded primary tumor samples composed of 119 SN-positive patients who underwent axillary lymph node dissection in National Kyushu Cancer Center. ROCK II expression was defined positive when there was strong intensity of cytoplasm staining.

(Results) ROCK II expression tended to be strong in invasive area, but weak in intraductal component. Of the 119 patients, 35 (29%) were determined to be positive for ROCK II expression. Patients with ROCK II positive tumor had significantly higher probability of non-SNs metastasis compared with patients with ROCK II negative tumor (20/35, 57% for positive; 28/84, 33% for negative, p=0.02). In multivariate analysis, positive ROCK II expression was significantly associated with non-SNs metastasis even after accounting for other predictive factors including tumor size, lymphovascular invasion, number of SNs metastasis and extra-capsule invasion (positive vs. negative, HR 2.6, p=0.04).

(Conclusion) These findings suggest that ROCK II expression can be a predictive factor for non-SNs involvement in breast cancer patients with SNs metastasis.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-27.
P3-07-32: The Role of Axillary Ultrasound in the Detection of Metastases from Primary Breast Cancers.
Authors: Yamashita M , Little E , Fraley J , Hovanessian-Larsen L , Sener SF
Published: June 2012

Background: The value of ultrasound (US) in the preoperative evaluation of axillary nodes has yet to be completely clarified. Preliminary experience with this technique in our institution was examined.

Methods: Patients with a radiographic or palpable abnormality of the breast had simultaneous breast and axillary US. The exams were performed by dedicated breast radiologists using a 12 MHz linear array transducer (HDI 5000: Philips Ultrasound). Results were reviewed for all patients with invasive cancers who were cN0 and had definitive surgical procedures between June 2006 and May 2008. Criteria for abnormal lymph nodes were loss of reniform shape, focal or diffuse cortical thickening, or eccentric/replaced fatty hilum. US-guided biopsies were done using a 16g spring-loaded core biopsy device (16g MD TECH SuperCore). Patients with positive axillary node biopsies bypassed sentinel lymph node biopsy (SLNB) and had axillary dissection, whereas those with sonographically normal nodes or benign/non-diagnostic biopsy results had SLNB at the time of definitive surgery.

Results: Of 128 patients diagnosed with invasive cancer, 23 (18%) had abnormal axillary US at the time of initial diagnosis. Biopsies were performed in 18 of the 23, of which 12 (67%) were malignant and 6 (33%) were benign. Ultrasounds were negative in 105 (82%) patients. SLNB was done in 110 patients: 103 with negative US; 4 patients with abnormal US but negative axillary biopsies; 2 patients with abnormal US but no core biopsies; and 1 patient with a positive US biopsy. SLNB was negative in 91 (83%) patients and positive in 19 (17%). The node-positive status was N1a in 14 patients and N1mic in 5. Axillary dissection was done in 32 (25%) of 128 patients, comprised of 11 patients with US-guided positive biopsies, 12 with positive sentinel nodes, 2 with US-guided negative biopsies, 2 with negative ultrasounds, 3 with unbiospied abnormal ultrasounds, and 2 with a false-negative SLNB. For determining axillary metastases with US, sensitivity was 16/31 (52%), specificity was 90/97 (93%), positive predictive value was 16/23 (69%), and negative predictive value was 90/105 (86%).

Conclusions: US examination was a valuable method of evaluating the axilla in newly diagnosed breast cancers. Of 32 patients having an axillary dissection, abnormal US eliminated the need for SLNB in 17 (53%). Patients with US-guided positive nodes were submitted to axillary dissection without SLNB. Therefore, we were unable to determine how often US identified an abnormal non-sentinel node, thus upstaging the axilla relative to SLNB alone. This question should be the topic of further clinical study.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-32.
P3-07-34: Occult Metastasis in Sentinel Node: Should This Affect the Clinical Decision Making? A Systematic Review and Meta-Analysis.
Authors: Valachis A , Nearchou A , Polyzos NP , Lind P , Berqvist J
Published: June 2012

Background: The role of occult metastases (micrometastasis or isolated tumor cells [ITC]) in sentinel lymph nodes (SLN) remains a field of debate and speculation. The purpose of this systematic review and meta-analysis was to investigate the prognostic relevance of occult metastases in SLN.

Methods: We searched PubMed, without year or language restriction through June 2011, for studies on patients with invasive breast cancer with micrometastasis or ITC in the SLN and presented Hazard Ratios (HR) on Overall Survival (OS) / Disease-Free Survival (DFS) or enough data for HR-calculation. We used fixed- or random-effects meta-analyses, as appropriate, to calculate pooled estimates of HR. Results: Fifteen studies were considered eligible. Of those, 3 studies were excluded due to the lack of data for HR-calculation. Both the presence of ITC (5 studies; 1264 patients with ITC) and micrometastasis (10 studies; 1093 patients with micrometastasis) were associated with worse DFS (pooled HR 1.29, 95% Confidence Interval [CI]: 1.09−1.52, P-value = 0.002 for ITC, pooled HR 1.45, 95% CI: 1.28−1.64, P-value < 0.001 for micrometastasis). No significant differences were observed regarding OS neither for the presence of ITC (5 studies; 877 patients with ITC; pooled HR 1.20, 95% CI 0.98−1.46) nor for micrometastasis (8 studies; 1094 patients with micrometastasis; pooled HR 1.36, 95% CI: 0.98−1.88).

Conclusion: Based on the current evidence, it seems that the presence of occult metastasis in SLN is of prognostic significance in regard to DFS. However, the clinical significance of this difference is questioned since it cannot be translated into differences in OS. In anticipation of randomized trials aimed to evaluating the optimal management of each category of tumor burden within SLN, current evidence suggest a limited clinical significance of occult metastases in SLN.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-34.
P3-07-35: Validation of Online Calculators To Predict Non-Sentinel Lymph Node Status in Sentinel Lymph Node-Positive Breast Cancer Patients.
Authors: Tanaka S , Sato N , Fujioka H , Takahashi Y , Kimura K , Iwamoto M
Published: June 2012

Purpose: Axillary lymph node dissection (ALND) is recommended for breast cancer patients with sentinel lymph node (SLN) metastasis, but further nodal disease is not always present. Several models exist for predicting non-sentinel lymph node (non-SLN) metastasis in SLN metastasis. This study evaluated and compared the predictive values of the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and the Stanford nomogram, which were conveniently available online, and clarified their usefulness for the micrometastasis or isolated tumor cell (ITC) subgroup.

Methods: Data from 89 patients with positive SLN biopsy who underwent ALND were used, including 59 patients with macrometastasis and 30 with micrometastasis/ITC. The predicted probability of non-SLN metastasis was calculated using a computerized model from the websites for each nomogram. Results were compared using area under the curve (AUC) of the receiver operating characteristics curve for each model. False-negative and false-positive rates were also calculated.

Results: AUC for the entire population was 0.701 with the MSKCC nomogram and 0.756 with the Stanford nomogram. AUCs of macrometastasis and micrometastasis/ITC were 0.680 and 0.469 with the MSKCC nomogram and 0.676 and 0.574 with the Stanford nomogram, respectively.

Conclusions: This independent comparison found no significant difference between the two nomograms. In our results, these nomograms could not reliably predict positive non-SLN in cases with SLN micrometastasis/ITC. Further validation in other patient populations is needed.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-35.
P3-07-40: Impact of the Sentinel Lymph Node Procedure on the Detection of Positive Lymph Nodes in Breast Cancer.
Authors: Smeets A , Yoshihara E , Laenen A , Wildiers H , Reynders A , Soens J , Paridaens R , Van Ongeval C , Floris G , Moerman P , Neven P , Christiaens M-R
Published: June 2012

Introduction: The objective of the sentinel lymph node (SLN) procedure in breast cancer is to perform an accurate axillary staging and provide good local control, while sparing the patients the morbidity of an axillary lymph node dissection (ALND). Since its routine clinical use, questions have been raised concerning the upstaging of a subgroup of node-negative patients and an increase in the overall percentage of node-positive patients.

The goal of our study was to investigate the impact of the SLN procedure on the detection of positive lymph nodes.

Patients and methods: We included 1119 consecutive breast cancer patients from one center (2007-2009) who underwent primary surgery for a breast cancer smaller than 5 cm diameter without clinical involvement of axillary lymph nodes. 31 patients had a bilateral breast cancer.

Logistic regression models were used to analyze the effect of various predictors on the presence of positive lymph nodes.

First, we fitted univariable models for a number of predictors of which the relationship with lymph node involvement was to be expected. (multifocality, tumor location in the breast, tumor size, LVI, ER, PR, Her-2, tumor grade, age and histologic subtype).

In a second stage, we fitted a multivariable model including the procedure (SLN biopsy or ALND) and the predictors that have been shown to be related to lymph node involvement in univariable analysis or for which this relationship has been suggested in the literature. The probability of finding positive lymph nodes was thus calculated in both groups correcting for relevant predictors of lymph node involvement.

Results: The SLN biopsy group includes 830 patients, the ALND group 320. Tumors in the ALND group are larger (mean 26.65 mm versus 18.43mm) and more frequently multifocal (24.44% versus 8.19%). 33% of patients in the ALND group were lymph node positive, 28% in the SLN procedure group. Univariable and multivariable analyses revealed that LVI, tumor size and multifocality are the most significant predictors of lymph node involvement (table 1). The AUC for the multivariate model is 0.754.

By comparing ALND en SLN biopsy an odds ratio (OR) of 0.7635 (95% confidence interval: 0.5334−1.0930) is observed, suggesting a higher probability of finding positive lymph nodes with SLN procedure. However, the difference between the procedures is not significant (p= 0.1404).

Conclusion: For comparable tumors, the chance of detecting positive lymph nodes is not lower when applying SLN procedure compared to ALND. The results even point in the direction of a higher detection rate with SLN.

However, care should be taken in making this conclusion given a non-significant result.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-40.
P3-07-48: Axillary Imaging with Dynamic MRI Following Subcutaneous Injection of Superparamagnetic Iron Oxide Nanoparticles.
Authors: Douek M , Johnson L , Parikh J , Charles-Eduards G , Hall-Craggs M
Published: June 2012

Background: Surgical axillary staging with sentinel node biopsy in clinically node negative patients is standard of care in the management of breast cancer. However sentinel node biopsy is associated with morbidity including a 5% risk of lymphoedema. Superparamagnetic iron oxide (SPIO) enhanced axillary MRI is a promising novel imaging modality that could be used to characterize sentinel nodes non-invasively. We evaluated subcutaneous SPIO enhanced axillary MRI for pre-operative axillary imaging.

Material and methods: Patients scheduled for sentinel node biopsy as part of surgical management of early breast cancer were invited to undergo pre-operative axillary MRI. All images were acquired on a 1.5T scanner using a surface coil. The initial 7 scans were acquired on a Siemens Avanto and the later scans on a Achieva MRI scanner (Philips Best, Netherlands). Following a T2-weighted morphological scan, patients were injected with 2ml of SPIO (4ml in the final 3 patients) subcutaneously into the circumareolar margin in the upper outer quadrant of the affected breast. Post injection, a slightly T2*-weighted dynamic scan was performed (gradient echo, TE = 1.53ms, TR=2.9ms, flip angle 7 degrees, 3mm slice thickness). In addition to the dynamic scan, in 16 patients, a T2 mapping sequence was performed at 10minutes and 120 minutes post injection (turbo spin echo, 8 equi-spaced TEs from 10 to 80ms, TR=2136ms, 3mm slices with an in plane resolution of 1.4×1.4mm). Image analysis was undertaken using Osirix (v3.8, 64-bit). Two consultant radiologists experienced at reading breast and axillary MRI reported all scans. Results: A total of 23 patients underwent axillary MRI with subcutaneous SPIO. Of these in 18 patients (78%), uptake of SPIO was seen in sentinel nodes and lymphatic tracts. At least 1 sentinel node was identified in 17 patients (74%). A total of 106 nodes were identified (4.6 ± 1.7 nodes per patient) and of these 40 demonstrated a significant drop in signal intensity following SPIO injection (1.7 ± 1.3 nodes per patient). All 3 involved nodes were seen to contain a metastatic deposit on MRI.

Discussion: Axillary MRI with subcutaneous SPIO injection is a robust method for imaging sentinel nodes. The normal node count of the axillary basin is lower than expected on histology, suggesting that only the larger nodes and those that take up SPIO are visualized on MRI.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-48.
P3-11-04: A Randomized Phase II Biomarker Study of Atorvastatin in Premenopausal Women at Increased Risk for Breast Cancer.
Authors: Wood ME , Kingsley F , Ellerton JA , Atkins JN , Grubs SS , Muss HB , Garber JE
Published: June 2012

Statins have been shown in epidemiological and laboratory studies to have breast cancer risk reduction properties. We evaluated the effect of atorvastatin on breast mammographic density (MD) and other breast cancer biomarkers in a small randomized placebo controlled trial.

Methods: Premenopausal women at increased risk for breast cancer (due to family history, BRCA positivity, prior biopsy history or history of chemoradiotherapy for Hodgkins disease) enrolled after signing informed consent and received either 40 mg of atorvastatin or placebo daily for 1 year. Biomarker assessment was performed prior to initiation and prior to completion of study medication. MD was determined using both Breast Imaging Reporting and Data System (BI-RADS) and the Visual Analogue Scale (VAS).

Results: 63 women were enrolled between 7/05 - 8/10 in this multi-institutional trial. 44 have completed study medication and 3 remain on study. 25% have withdrawn; 17% of them for toxicity/side effects. Of those completing the study; mean age was 47 (range 35–50), 96% Caucasian, mean BMI 26.8. 66% had a strong family history (2% were BRCA+), 27.7% had ADH/LCIS. We present analysis of MD in the first 37 women completing study drug. The two treatment groups were well balance for age, BMI, risk factors and baseline density. Mean density by VAS was 31.6% at study entry and 32.4% at end of treatment. There was no different in change in density over time between atorvastatin and placebo using either BIRAD or VAS; controlling for BMI did not change results. Futility analysis demonstrates low probability of a significant difference between treatment groups and the study was closed.

Conclusions: In this multi-institutional randomized prospective clinical trial of premenopausal women at increased risk for breast cancer we have failed to demonstrate a significant effect of atorvastatin on mammographic density. There are several possible reasons for this relating to: the study population, method of density determination and/or biomarker analyzed. While the primary aim of this study (MD) was not met we have shown that biomarker studies can be done in a multi-institutional setting. Further biomarker evaluation may prove informative.

Funding: This study is sponsored by grants from Breast Cancer Research Foundation and Cancer and Leukemia Group B to M. Wood.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-11-04.
P3-11-05: An Efficient Resource To Accelerate Research into the Cause and Prevention of Breast Cancer: The Love/Avon Army of Women.
Authors: Love SM
Published: June 2012

Background

It is well established that more research into the cause and prevention of breast cancer is needed. While many studies are done in cell lines and laboratory animals, translation of findings to women often falters due to perceived difficulty in recruiting women for research. The Dr. Susan Love Research Foundation received a grant from the Avon Foundation to form the Love/Avon Army of Women (AOW); an on-line recruitment resource launched in 2008, designed to partner one million women with the research community in an effort to accelerate breast cancer research.

Methods: Researchers submit a proposal to the AOW Scientific Advisory Committee. If a study is accepted, a mass e-mail describing the study procedures and inclusion/exclusion criteria is sent to the entire AOW database. Women sign up at www.armyofwomen.org to join and receive AOW e-mails about breast cancer research studies. Women self select based on interest and study criteria, and undergo a secondary on-line screening before contact information is passed on to the researcher for the enrollment process.

Results: Over 356,000 women have signed up, including survivors and healthy women, ranging from ages 18 to 100, representing all 50 US states and 49 countries. To date, the AOW has recruited for 48 studies, both regional and national, that vary from biomarker and circadian rhythm research to psycho-social and quality of life studies. With over 54,000 AOW members having participated in the research process, this method of recruitment has been found to be effective and efficient. The diversity of the AOW members has proved beneficial for many studies, such as those needing to enroll racial/ethnic minorities, women of varying sexual orientations, or young survivors.

Nine studies were closed to enrollment within the first 48 hours after accruing all subjects while others were very quickly over-enrolled by 5–10%. A urine biomarker study in search of healthy women and breast cancer survivors closed within eight hours, after 2,076 women signed up, representing a 58% over-enrollment. This overwhelming response has led many researchers to seek additional funding to increase their statistical significance and accommodate all eligible subjects.

Conclusions: The AOW has proved to be a successful resource for scientists to accelerate accrual, expand the number and diversity of their subject population and to obtain exactly the type of specimens they need when they need it. This partnership between women and scientists has revolutionized research and accelerated efforts to eradicate breast cancer.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-11-05.
P3-13-01: Boost Radiation Therapy Not of Value in Reducing IBTR of Invasive or Noninvasive Breast Cancers for Patients with DCIS: Results from the NSABP B-24 Trial.
Authors: Julian TB , Vicini FA , Costantino JP , Arthur DW , Kidwell KM , Land SR , Mamounas EP , Wolmark N
Published: June 2012

Background: Whole breast irradiation therapy following lumpectomy for invasive breast cancer (IBC) or noninvasive breast cancer (DCIS) significantly reduces the risk of local recurrence. Boost radiation therapy to the tumor bed has been proven to additionally lower the risk of recurrence for IBC. The benefit of boost therapy in patients with DCIS is less certain. We carried out a review of the NSABP B-24 trial to assess the benefit of boost therapy.

Methods: After lumpectomy and radiation therapy, 1804 women with DCIS were randomly assigned to placebo (902) or tamoxifen (902). Whole breast irradiation therapy (50 Gy) was mandatory. Boost radiation therapy was optional, and boost status was known for 1,569 patients. Of these, 1392 patients (86.97%) were identified as having all data sufficient for multivariate analysis. Of these, 613 received boost therapy ranging from 1 Gy −20 Gy, with 81.5% receiving 10 Gy. Mean time of follow-up was 161 months.

Results: Patients who received boost radiation therapy were more likely to be younger (p=0.04), have positive margins (p=0.007), and be more likely to have comedo necrosis (p=0.03). Multivariate analysis identified only treatment (tamoxifen vs placebo) (HR=0.74, 95% CI=0.57−0.98, p=0.034), age (≥ 50 verses < 50) (HR=0.47, 95% CI=0.36−0.61, p<0.0001), and margin status (positive vs negative) (HR: 1.79, 95% CI= 1.31−2.43, p<0.001) as significant predictors for ipsilateral breast tumor recurrence (IBTR). Boost had no significant effect on IBTR (HR=0.87, 95% CI=0.66−1.15, p=0.33). The lack of boost effect applied to both invasive (HR=0.86, 95% CI=0.58−1.27, p=0.44) and noninvasive IBTR (HR=0.89, 95% CI=0.60−1.33, p=0.56).

No interaction was seen between boost and treatment, age, margin status, or comedo necrosis.

Conclusion: In NSABP B-24, the addition of boost radiation therapy was not found to be of value in reducing IBTR of invasive or noninvasive breast cancers for patients with DCIS.

Supported by PHS grants NCI-U10-CA-69651, NCI-U10-CA-12027, and NCI P30-CA-14599 from the US NCI and AstraZeneca.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-13-01.
P3-13-04: Functional and Cosmetic Outcomes Following Post-Mastectomy Irradiation with Tissue Expander/Implant Reconstruction.
Authors: Baschnagel A , Shah C , Wilkinson JB , Dekhne N , Margolis J , Arthur DW , Vicini F
Published: June 2012

Purpose: To examine the rate of breast reconstruction failure and cosmetic outcomes following post-mastectomy radiation therapy (PMRT) with temporary tissue expander or implant in place.

Methods and Materials: Ninety-four patients with 95 primary breast malignancies underwent mastectomy and immediate tissue expander reconstruction followed by PMRT. Ninety tissue expanders and five implants were irradiated. All patients received a dose of 5,400 cGy given in 180 cGy fractions. Twenty-one patients (22%) received tangents alone and seventy-four patients (78%) were treated with tangents and a supraclavicular field via a mono-isocentric technique. Bolus was used in 91 patients (96%). Eighty-eight patients (93%) received chemotherapy and 78 patients (82%) received endocrine therapy.

Results: With a median follow up of 22.4 months, nineteen patients (20%) developed a reconstruction failure. Ten patients lost their tissue expanders with a median time to reconstruction failure of 7 months (range 3–9 months) while ten patients lost their permanent implant with a median time to loss of 19 months (range 9–31 months) following PMRT. The one and two-year actuarial rate of reconstruction failure was 11.2% and 24.9%, respectively. The most common cause of failure was infection (37%), followed by skin break down (21%), extrusion of expander or implant (16%), fibrosis/eschar (11%), trauma (11%) and pain (5%). Out of the 19 failures, eight patients were salvaged with an autologous flap reconstruction. Univariate analysis was performed to examine the association between age, chemotherapy, hormonal therapy, smoking status, hypertension, diabetes, menopause status, weight and the use of a third supraclavicular RT field on reconstruction failure. However no risk factors were found to be associated with reconstruction failure. In patients who did not have reconstruction failure, good/excellent cosmesis was observed in 79% of patients and fair/poor cosmesis was observed in 21% of patients.

Conclusions: In our series of women with a high risk of recurrence, PMRT with a tissue expander in place followed by a prosthetic implant provides good cosmesis in the majority of women with an acceptable risk of expander or implant loss.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-13-04.
P3-13-09: Impact of Estrogen Receptor Negativity on Clinical Outcomes Following Accelerated Partial Breast Irradiation.
Authors: Wilkinson JB , Baschnagel A , Shah C , Amin M , Nadeau L , Mitchell CK , Wallace MF , Chen PY , Grills IS , Martinez AA , Vicini FA
Published: June 2012

Purpose: To determine the impact of estrogen receptor (ER) negativity on clinical outcomes for patients treated with Accelerated Partial Breast Irradiation (APBI).

Materials/Methods(s): We evaluated 506 consecutive patients treated with interstitial brachytherapy (n= 199), balloon-based brachytherapy (n=203), and 3D-CRT (n=104). ER negative (ERN) status was assigned using the traditional definition of an ER nuclear IHC stain < 10%, which corresponds to an Allred/NSABP staining score of < 2. 63 patients (12.5%) were ER negative and 443 (87.5%) were ER positive (ERP). Patient demographics and clinical outcomes (IBTR, RNF, DM, DFS, CSS, OS) were analyzed for each group.

Results: The two groups had similar patient characteristics. Tumor sizes were slightly larger for the ERN group at 11.9mm vs. 10.7mm, although this was not statistically significant (p=0.14). No differences were seen in median age (63 vs. 64 years, p=0.36), rate of HER-2/neu overexpression (83% vs. 91%, p=0.11), or lymph node positivity (6% vs. 9%, p=0.55) between the ERN vs. ERP groups, respectively. There were an equal distribution of invasive ductal carcinoma (ERN n=55, 87%; ERP n=387, 87%) and DCIS (ERN n=8, 13%; ERP n=56, 13%) patients within each group. The use of chemotherapy (55% vs. 15%, p<0.001) and nuclear grade (71% vs. 12%, p<0.001) were higher in the ERN vs. ERP cohort. With a mean follow up of 6.1 years, the 5-year actuarial rates of ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), and distant metastasis (DM) for the entire cohort were 1.8%, 0.6%, and 3.2%. Although this was not statistically significant, ERN patients appear to have an increased rate of local failure than patients with ERP histology (4.0% vs. 1.5%, p=0.13). Rates of RNF and DM were, however, significantly higher for the ERN group (RNF: 4.9% ERN vs. 0% ERP, p<0.001; DM: 12.1% ERN vs. 2.0% ERP, p<0.001). Although there was no difference in overall survival at six years (86% vs. 90%, p=0.67), we observed a shorter disease-free survival (86.4% vs. 96.5%, p= 0.01) and cause-specific survival (90% vs. 98%, p=0.01) for the ERN vs. ERP groups.

Conclusion: The ER negative phenotype of early-stage breast cancer may have a decreased rate of locoregional control. We observed a higher rate of DM with reduced disease-free and cause-specific survival in ER negative cases, emphasizing the importance of systemic therapy and careful, long-term follow up for these patients. Prospective study of this histologic subtype with a larger cohort of patients is needed to substantiate these findings.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-13-09.
P3-14-07: Relative Risk of Recurrence (RR) over Time in ER Positive and Negative T4 Breast Cancer Patients Achieving Less Than pCR (<pCR) after Primary Chemotherapy: A Reversal Trend of Recurrence beyond 60 Months after Diagnosis.
Authors: Ionta MT , Atzori F , Pusceddu V , Notari F , Valle E , Guerzoni D , Chiappe A , Marongiu M , Minerba L , Massidda B
Published: June 2012

Background

It is widely assumed that patients (pts) who achieve a pCR have a good prognosis and better outcomes compared with pts with <pCR, regardless of hormone receptor status. Emerging data suggest that achieving <pCR identifies a heterogeneous group with different risks of recurrence and death, being ER negative the subgroup with the worst prognosis.

Aim of our study was to evaluate the relative risk of recurrence (RR) over time in ER-positive (ER+) and ER-negative (ER-) <pCR patients.

Material and Methods: We analyzed 139 consecutive <pCR T4 pts, of whom 85 were ER+ (cut-off 10%) and 54 were ER-. Median age was 53 y ( range 29–73). Median follow up was 137 months (range 8–233). All pts received primary anthra-based chemotherapy with or without taxanes followed by endocrine therapy for 5 years, if hormone receptor positive. We examined the RR of recurrence at 0–24, 25–60, 61–120 and beyond 120 months (m) interval after diagnosis.

Results: For all 139 pts, the total number of pts with recurrence was 95 (68%), 54 (63%) in ER+ and 41 (76%) in ER-.tumors. For the entire group and both in ER+ and in ER-, the RR of recurrence was greatest for the interval between 0–24 months, then decreased rapidly in ER- and slowly in ER+ through the 25–120 m interval. For the 0–24 m and 25–60 m intervals the RR of recurrence was higher for ER-pts and after 60 m it crossed and beyond 60 m the RR of recurrence was higher in ER+ than in ER- pts. Notably, beyond 120 months we observed a little second peak of recurrence, higher in ER+ (7) than in ER- (3) pts. Nine of these 10 relapses occurred between 120 to 180 m interval, 7 in ER+ (13%) and 2 in ER- (5%) subgroup. In the first 24 m ER- pts were 86% more likely to relapse compared with ER+, vice versa between 61–120 and beyond 120 m intervals, ER- pts were 19% and 18% less likely to relapse, respectively, compared with ER+ pts.

Conclusions: The present study confirmed the previous reports which showed unfavorable prognosis of the <pCR patients with negative ER status, due to their significantly higher relative risk of recurrence between 0 to 60 months interval. The ER+ recurrences occurred more frequently in late follow-up. A reversal of recurrence between ER positive and negative patients beyond 60 months after diagnosis was detected. The fact might indicate the importance of long term adjuvant hormone therapy for T4 ER positive breast cancer patients with <pCR after primary chemotherapy.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-07.
P3-14-11: Comparison of Two Nomograms To Predict Pathologic Complete Response to Neoadjuvant Chemotherapy – Evidence That HER2 Positive Tumors Need Specific Predictors.
Authors: Rouzier R , Frati A , Coutant C , Bezu C , Antoine M , Uzan S , Chopier J , Chereau E , Gligorov J
Published: June 2012

Aim: The purpose of this study was to compare two different nomograms to predict pathologic complete response (pCR) to preoperative chemotherapy in an independent cohort of 200 patients with breast cancer. The first model was the MDACC nomogram published in 2005 and the other one was a nomogram based on the number of preoperative courses, Ki-67 and steroid hormone receptors expression published by Colleoni et al. in 2010

Patients and methods: Data from 200 patients with breast carcinoma treated with preoperative chemotherapy and operated at Tenon Hospital from 2001 to 2009 were collected. We calculated pCR rate predictions with the two nomograms and compare those predictions with outcome. Patients received between 4 and 8 course of anthracycline/taxanes based chemotherapy. More than 90% of patients with HER2 positive tumors received concomitant trastuzumab with taxanes. Model performances were quantified with respect to discrimination (evaluated by the areas under the receiver operating characteristics curves (AUC)) and calibration.

Results: In the entire population, the AUC for the MDACC nomogram and the Colleoni nomogram were respectively 0.74 and 0.75. Both of them underestimated the pCR rate (p=0.02 and 0.0005). When excluding patients treated with trastuzumab, the AUC were 0.78 for both of them with no significant difference between the predicted and the observed pCR (p=0.14 and 0.15). When analyzing the specific population treated with trastuzumab as preoperative treatment, the AUC for the MDACC nomogram and the Colleoni nomogram were respectively 0.52 and 0.53.

Conclusion: The MDACC and the Colleoni nomograms are accurate to predict the probability of pCR after preoperative chemotherapy in HER2 negative population but did not correctly predict pCR in HER2 positive patients who received trastuzumab. This suggests that response to preoperative chemotherapy including trastuzumab is biologically driven and that a specific nomogram or predictor for HER2 positive patients has to be developed.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-11.
P3-14-24: A Phase II Trial of TS-1 and Docetaxel Followed by 5-FU/Epirubicin/Cyclophosphamide (FEC) as Preoperative Treatment in Women with Stage II/III Breast Cancer.
Authors: Hayashida T , Jinno H , Sakata M , Takahashi M , Kitagawa Y
Published: June 2012

Background: TS-1 is an oral anticancer drug, composed of tegafur, gimestat and otastat potassium in a molar ratio of 1:0.4:1, based on the biochemical modulation of 5-Fuorouracil. In vivo xenograft model showed a synergistic effect of combination chemotherapy with TS-1 and docetaxel through down-regulation of dihydropyrimidine dehydrogenase (DPD). (Suto et al, Oncology Reports 2006) The sequential combination of anthracycline and taxane is a standard of care in the preoperative setting, as well as the adjuvant setting. This study's purpose was to determine the efficacy of TS-1 and docetaxel followed by fluorouracil/epirubicin/cyclophosphamide (FEC) in the preoperative setting.

Patients and Methods: Patients with stage II/III breast cancer received 4 cycles of TS-1 (TS-1 80 mg/m2 on days 1–14 and docetaxel 40 mg/m2 on day 1 every 3 weeks), followed by 4 cycles of FEC (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2 on day 1 every 3 weeks). The tumor objective response was assessed by both caliper and ultrasound. Primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints were the clinical response rate, adverse drug reactions, and the breast conservation rate.

Results: From November 2009 to December 2010, 39 patients were enrolled and 38 patients were assessable for clinical and pathologic responses. The overall response rate (caliper) was 81.5% and ultrasound response rate was 76.3%. The pCR rate was 13.2% (5/38). The breast-conserving rate in patients whose tumor size was 3 cm or smaller was 92.9%, and 54.5% of patients whose tumor size was larger than 3 cm underwent breast-conserving surgery. The ratio of Ki-67 positive cell and progesterone receptor (PgR) status were significantly correlated with pCR. Grade 4 neutropenia was observed in a patient (2.6%) at the first cycle. The most common grade 3/4 non-hematologic adverse event was hand-foot syndrome, observed in 3 patients (7.9%). One patient (2.6%) showed grade 3 diarrhea.

Conclusions: These results indicate that the sequential combination of TS-1 and docetaxel followed by FEC is a well-tolerated, effective neoadjuvant treatment for stage II/III breast cancer.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-24.