bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-10-15: Evaluation of Prognostic and Predictive Performance of Breast Cancer Index and Its Components in Hormonal Receptor-Positive Breast Cancer Patients: A TransATAC Study
Authors: Sgroi DC , Sestak I , Zhang Y , Erlander MG , Schnabel CA , Goss PE , Cuzick J , Dowsett M 
Published: August 2014

Abstract
Background: The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial compared the efficacy and safety of 5 years of anastrozole with tamoxifen as adjuvant treatment for postmenopausal women with localized HR+ breast cancer. At a median follow-up of 10 years, a statistically significant improvement with anastrozole vs. tamoxifen for disease-free survival, time to recurrence and time to distant recurrence was observed. The HOXB13:IL17BR gene expression ratio (H/I) quantifies recurrence risk in ER positive (ER+) breast cancer patients and is predictive of benefit from endocrine therapy. Molecular Grade Index (MGI) is a five-gene index that provides quantitative and objective molecular assessment of tumor grade and proliferative status. Breast Cancer Index (BCI) combines H/I and MGI into a continuous risk model that provides a likelihood of distant recurrence in patients treated with endocrine therapy, and efficacy from neoadjuvant chemotherapy. In the current analysis, evaluation of the prognostic and predictive performance of BCI, H/I and MGI in the ATAC study cohort was conducted.
Methods: Under the TransATAC protocol, formalin-fixed, paraffin-embedded (FFPE) blocks of primary tumor were collected from HR+ patients from each monotherapy arm. The current study examined samples collected from the United Kingdom, which constituted 79% of the collection. RNA extracted from 1102 samples from the TransATAC study was amplified, converted to cDNA and subjected to RT-PCR with primers and probes to HOXB13, IL17BR, BUB1A, CENPA, NEK2, RACGAP1 and RRM2. H/I, MGI and BCI were calculated and risk groups were determined using pre-specified cutpoints.
Results: Of 1102 tumor specimens assayed, 29 failed QC criteria, leaving 1073 samples for analysis. Detailed results on the prognostic and predictive performance of BCI, H/I and MGI will be presented. Data on whether BCI and its components provided independent prognostic information in the presence of classical variables, their prognostic value for risk of late recurrence, interaction by treatment arms, and comparative performance vs other models will also be discussed.
Discussion: The ATAC trial has established the long-term efficacy and safety of anastrozole over tamoxifen as initial adjuvant treatment for post-menopausal early stage breast cancer patients. Continued efforts are needed to improve on quantification of residual risk in patients who were treated with endocrine therapy to guide decision-making in selecting additional adjuvant chemotherapy and/or administering extended endocrine treatment. This study will help to establish the strategy to more effectively select patients for adjuvant therapies.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-15.
Abstract P2-11-04: Chemotherapy Induces Neuroinflammation and Cognitive Deficits in Female Mice
Authors: Jarrett BL , Lustberg MB , Hinzey A , Stuller KA , Shapiro CL , DeVries C 
Published: August 2014

Abstract
Introduction: Advances in cancer detection and treatment have substantially increased the survival rate for breast cancer patients. Chemotherapeutic drugs, particularly anthracyclines, have potentially toxic side effects in the brain- impacting memory, processing time and verbal fluency. More than 30% of patients undergoing chemotherapy for breast cancer report cognitive deficits during and after treatment. Despite the high incidence and significant impact on quality of life, little is known about the cause of the cognitive deficits and no effective treatment currently exists. Our hypothesis is that chemotherapy-induced neuroinflammation impairs cognition.
Methods: Adult female BALB/C mice were ovariectomized and then two weeks later injected intravenous (IV) with a single dose of chemotherapy (45 mg/m2 doxorubicin + 450 mg/m2 cyclophosphamide) or vehicle (n = 10–12/group). The mice were trained for three trials per day across six days in the Barnes Maze, a well-characterized spatial memory task.
Results: Both the chemotherapy-treated and vehicle-treated mice were able to acquire the task by the final day of training. However, the vehicle-treated mice reached asymptotic performance after fewer training sessions than the chemotherapy-treated mice. Furthermore, the chemotherapy-treated mice took significantly longer to find the escape box than the vehicle-treated mice on training days 2–5 (p &lt; 0.05). In contrast, there were no group differences in overall locomotor activity level, suggesting that the observed difference in maze performance was not due to a fatigue. (p &gt; 0.05) In addition, chemotherapy increased proinflammatory cytokine expression (TNF-α, IL-1β, and IL-6) in the hippocampus (p &lt; 0.05), a region of the brain that is critical for spatial learning and memory. Likewise, microglia from chemotherapy-treated mice exhibited increased expression of MHCII and CD80 relative to vehicle-treated mice (p &lt; 0.05), thereby suggesting a proinflammatory phenotype.
Conclusions: Together, these data suggest that the administration of doxorubicin and cyclophosphamide in doses that are approximately 25% lower than the typical dose for women treated for breast cancer, produce neuroinflammation, including microglia activation, increased proinflammatory cytokine expression and concomitant cognitive deficits in female mice. Additional studies will establish whether a causal relationship exists between chemotherapy-induced neuroinflammation and cognitive deficits. Identifying the mechanism through which chemotherapy induces cognitive deficits is the first step toward designing therapeutic interventions.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-04.
Abstract P2-11-06: Mortality among offspring of women diagnosed with breast cancer; a population based study
Authors: Verkooijen HM , Ang X , Liu J , Czene K , Salim A , Hartman M 
Published: August 2014

Abstract
Introduction: Survival after breast cancer has improved substantially over the past decades. As a result, an increasing number of breast cancer survivors is starting or extending their family post-diagnosis. We evaluated mortality risks of offspring from women with a history of breast cancer.
Methods: From the Swedish Multi-Generation Register and the Cancer Register we identified all 63,205 children whose mother had ever been diagnosed with invasive breast cancer. For these children, we calculated relative mortality risks as compared to the background population (Standardized Mortality Ratios [SMRs]). We compared SMRs according to the mother's parity status at diagnosis and timing of birth in relation to time of diagnosis, i.e. before (&gt;1 year before), around (between 1 year before and 1 year after) and after (&gt;1 year after) diagnosis.
Results: Children born around their mother's breast cancer diagnosis had an increased mortality risk as compared to the background population (SMR 2.70 95% CI [1.64–4.44]). This risk was particularly high for first-born children (SMR 11.07 (95% CI [2.09–27.13]), who had an absolute excess risk of 6.4% to die before the age of 5 years. Children born more than one year before or after their mother's breast cancer diagnosis had similar mortality risks as the background population.
Conclusion: Children born around their mother's breast cancer diagnosis have significantly increased mortality risks. Offspring of nulliparous women have a particularly high relative mortality risk, suggesting that pregnant breast cancer patients may be keen to keep their first child in spite of potential treatment toxicity.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-06.
Abstract P2-13-01: Impact of Body Mass Index (BMI) on the efficacy of aromatase inhibitors to suppress estradiol serum levels in postmenopausal patients with early breast cancer: a prospective proof of principle
Authors: Pfeiler G , Königsberg R , Hadji P , Fitzal F , Maroske M , Ban G , Zellinger J , Exner R , Seifert M , Singer C , Gnant M , Dubsky P 
Published: August 2014

Abstract
Background: BMI impacts on the efficacy of aromatase inhibitors (AIs) regarding disease outcome in patients with early breast cancer. We hypothesized that this clinical impact of BMI is driven by the inability of AIs to suppress estradiol (E2) serum levels to the same low level in obese compared to non-obese patients.
Methods: 68 postmenopausal ER positive patients with breast cancer, scheduled to receive anastrozole or letrozole as adjuvant endocrine treatment were prospectively included in this study. Serum was taken before (T1) and 3 months after start with aromatase inhibitors (T2). Serum levels of FSH, LH, E2, glucose and insulin were analyzed immediately in the clinical routine lab and in a dedicated central lab able to measure E2 in serum at low concentrations with high sensitivity.
Results: 40 patients were normal - or overweight (non-obese; BMI 18.5–29.9 kg/m2) and 28 patients were obese (BMI ≥ 30 kg/m2). A weak non-significant correlation between BMI and baseline E2 serum levels (r = 0.2, p = 0.2) translated into a strong negative, highly significant correlation between BMI and baseline FSH (r = −0.6, p &lt; 0.01). After 3 months of AI treatment, a moderate correlation between BMI and E2 serum levels (r = 0.35, p = 0.05) and a moderate negative correlation between BMI and FSH (r = −0.34, p = 0.05) could be observed. Aromatase inhibitors significantly suppressed E2 serum levels in non-obese (T1: 18.9 pg/ml, T2: 9.0 pg/ml, p &lt; 0.01) as well as in obese patients (T1: 20.2 pg/ml, T2: 12.5 pg/ml, p &lt; 0.05). In addition an increase in FSH serum levels was observed in obese (T1: 50.0 mIU/ml, T2: 65.5 mIU/ml, p &lt; 0.01) but not in non-obese (T1: 84.0 mIU/ml, T2: 84.6 mIU/ml) patients. However, after 3 months of AI treatment, E2 levels of obese patients were not at the same low level when compared to non-obese patients (E2 obese: 12.5 pg/ml vs. E2 non-obese: 9.0 pg/ml, p = 0.1). This difference translated into significantly lower FSH serum levels in obese compared to non-obese patients (FSH obese: 65.5 mIU/ml vs. FSH: 84.6 mIU/ml, p &lt; 0.01). The significant effects of BMI on FSH serum levels could be detected both in the routine - as well as in the dedicated central lab.
Conclusion: AIs are less efficient at suppressing E2 serum levels in obese when compared to non-obese women. The observed effect may contribute to the survival disadvantage of obese patients in adjuvant AI trials. FSH serum levels should be validated as high sensitive surrogate parameters for estradiol serum level suppression by aromatase inhibitors in postmenopausal patients with breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-13-01.
Abstract P3-07-10: Effect of lifestyle and single nucleotide polymorphisms on breast cancer risk: A case-control study in Japanese women
Authors: Mizoo T , Taira N , Nishiyama K , Nogami T , Iwamoto T , Motoki T , Shien T , Matuoka J , Doihara H , Ishihara S , Kawai N , Kawasaki K , Ishibe Y , Ogasawara Y 
Published: August 2014

Abstract
[Background] Lifestyle, including diet and physical activity, and birth/breastfeeding history are known to affect the risk for breast cancer. A correlation between single nucleotide polymorphisms (SNPs) and breast cancer risk has also been suggested in some reports, but the gene-environment interaction with breast cancer risk has not been examined widely.
[Methods] The subjects were 476 breast cancer patients and 528 controls who attended a health check and had no history of breast cancer. Lifestyle was examined using a questionnaire with 48 questions about diet, physical activity, smoking habits, alcohol intake, and birth/breastfeeding history, etc. Based on past reports, we analyzed 6 SNPs (TNRC9-rs3803662, LSP1/11q-rs3817198, MAP3K1-rs889312, 8q24-rs13281615, 5p12-rs981782, and TGFβ1-rs1800470) using blood samples, and calculated age-adjusted odds ratios in a multiple logistic regression analysis.
[Results] The study was performed from December 2010 to November 2011. Lifestyle factors (age-adjusted odds ratio, [95% confident interval]) found to have a significant correlation with development of breast cancer included BMI (1.041, [1.00–1.08]), smoking history (2.28, [1.45–3.65]), small number of births (1.18, [1.05–1.34]), no exercise during leisure time (1.36, [1.06–1.77]), low intake of green and yellow vegetables (1.69, [1.01–2.85]), and low intake of mushrooms (1.58, [1.05–2.39]). Stratified analysis based on menopause status showed that smoking history (1.85, [1.00–3.49]) and low intake of green and yellow vegetables (2.5, [1.03–5.88]) were significant risk factors before menopause, and that smoking history (2.28, [1.45–3.65]), low intake of green and yellow vegetables (2.24, [1.09–4.68]), no exercise during leisure time (1.67, [1.19–2.36]), small number of births (1.49, [1.25–1.78]), and no breastfeeding history (1.03, [1.01–1.06]) were significant risk factors after menopause. The results of SNP analysis suggested that TNRC9-rs3803662 was a significant risk factor in women before menopause (2.29, [1.25–4.25]). However, in multivariate analysis including lifestyle factors and SNPs, only smoking history emerged as a significant risk factor in women before menopause.
[Conclusion] A correlation between lifestyle and breast cancer risk was found in this study, consistent with previous findings. Lifestyle and environmental factors such as births and breastfeeding may be more important than SNPs as risk factors for breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-07-10.
Abstract P5-18-15: Molecular effects of lapatinib in HER2 positive ductal carcinoma in situ (DCIS)
Authors: Estevez LG , Suarez A , Calvo I , Garcia E , Miro C , Durán H , Quijano Y , Perea S , Herrero M , Lopez-Rios F , Hidalgo M 
Published: August 2014

Abstract
Background: HER2 amplification is frequent in DCIS and is associated with poor prognosis features. This study aimed to determine the molecular effects in Ras/Raf/MAK and PI3K/AKT signaling pathway of the HER2 inhibitor lapatinib in patients with HER2 positive DCIS as well as correlation with radiological and pathological response.
Patients and Methods: Patients (pts) with HER2 positive DCIS received 1500 mg daily of lapatinib for 4 consecutive weeks prior to surgical resection. Changes in tumor volume were evaluated by MRI. The molecular effects of lapatinib on apoptotic level (TUNEL), cell proliferation (Ki67) and HER2 signaling pathway were determined in pre and post-treatment tumor biopsies.
Results: A total of 20 pts were included. Lapatinib was well tolerated with only minor and transient side effects reported. The agent effectively modulated HER2 signaling by affecting cell cycle kinetics through decreasing cytoplasm pERK1 in 11 pts with no change or slight increase activation in 5 pts. Of those 11 pts: eight had parallel inactivation of pHER2, two pts had paradoxical activation of pAkt and three pts had an increase in apoptotic level. In addition, seven pts also presented with decrease in MRI signal intensity and tumor size.
Conclusions: Four weeks of lapatinib for patients with HER2-positive DCIS result in significant antiproliferative changes through RAS/MAPK signaling pathway together with a decrease in MRI signal.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-15.
Abstract P6-05-02: Endocrine biomarkers in response to AR-inhibition with bicalutamide for the treatment of AR(+), ER/PR(−) metastatic breast cancer (MBC) (TBCRC011)
Authors: Gucalp A , Tolaney S , Isakoff SJ , Ingle J , Liu MC , Carey L , Blackwell KL , Rugo H , Nabell L , Forero A , Stearns V , Momen L , Gonzalez J , Akhtar A , Giri DD , Patil S , Feigin KN , Hudis CA , Traina TA 
Published: August 2014

Abstract
Background: Our group and others have identified a subset of ER/PR(−) breast cancers characterized by expression of the androgen receptor (AR) and androgen-dependent growth (Doane 2006). We conducted a proof-of-concept multicenter phase II study to test the efficacy of the AR-antagonist, bicalutamide for the treatment of AR(+) ER/PR(−) MBC (NCT00468715). Results of the primary endpoint, clinical benefit rate (CBR), were presented at ASCO (Gucalp 2012). Data for the impact of bicalutamide on circulating hormone levels in women are limited. Elevations in serum testosterone (T) and estradiol (E) have been observed for men treated with bicalutamide. We hypothesized comparable patterns of change in circulating endocrine markers in response to bicalutamide for women with MBC.
Methods: Patients (pts) with AR(+) (IHC ≥10%), ER/PR(−) (IHC &lt;10%) MBC were eligible for treatment (tx) if ECOG performance status ≤2 and normal organ function regardless of menopausal status. There was no limit to prior tx except prior trastuzumab required if HER2(+). Tx consisted of bicalutamide 150mg orally daily in 28-day cycles (C). Toxicity assessed q4 weeks, response q12wks. Primary endpoint was CBR. Peripheral blood was collected for total and free T, E and sex hormone binding globulin (SHBG) at baseline, start of C2 (C2) and at end of study (EOS). Standard institutional assays were used. A Wilcoxon signed-rank test was done to compare baseline to C2 and EOS values.
Results: 26 patients with AR(+) ER/PR(−) MBC were treated on study. Evaluable number (n) of pts at baseline, C2 and EOS are 26, 26 and 19 respectively. Two pts remain on study. Menopausal status: pre=2, post=24. Baseline median total and free T and estradiol were consistent with expected norms, however a wide range was observed (Table). There were no significant differences observed for median free T, total T, E or SHBG between baseline and C2 or baseline and EOS. Changes in hormone levels could not be stratified by menopausal status or response to bicalutamide given small sample size. Given the wide range of baseline values, we examined the percent change for each endocrine biomarker from baseline to C2 and EOS. As shown in the Table, there was no difference in median percent change observed across time points for each biomarker.

Conclusions: No discernible patterns of change in T, E or SHBG were observed in response to bicalutamide therapy when given to women for the treatment of AR(+), ER/PR(−) MBC. These circulating hormones require further evaluation for use as a pharmacodynamic marker.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-05-02.
Abstract PD07-05: A randomized controlled trial comparing zoledronic acid plus chemotherapy with chemotherapy alone as a neoadjuvant treatment in patients with HER2-negative primary breast cancer
Authors: Hasegawa Y , Kohno N , Horiguchi J , Miura D , Ishikawa T , Hayashi M , Takao S , Kim SJ , Tanino H , Miyashita M , Konishi M , Shigeoka Y , Yamagami K , Akazawa K 
Published: August 2014

Abstract
Background: Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate, and it induces osteoclast apoptosis and inhibits bone resorption by inhibiting the mevalonate pathway. ZOL has also been found to have antitumor effects that include an angiogenesis inhibiting action, an inhibitory effect on tumor cell adhesion to bone, an inhibitory effect on invasion of the extracellular matrix, and activation of a gdT cells. In addition, it has been found to have a synergistic anti-proliferative effect when used in combination with antitumor drugs.
In this study we investigated the pathological complete response (pCR) rate when ZOL is added to anthracycline followed by taxane to treat T2 and T3 breast cancer patients as a neoadjuvant chemotherapy.
Methods: Women with resectable invasive StageIIA-IIIB (T ≥3 cm or T ≥2 cm and lymph node positive) breast cancer who are HER-2-negative, between 20 and 70 years of age, and ECOG PS 0–1 were eligible.
Patients with distant metastasis, patients who have had received chemotherapy, hormone therapy, or radiotherapy for breast cancer, patients with serious complications, such as heart disease or an infection, patients with a complicating dental or jaw infection or traumatic condition of the teeth, and patients with a history of treatment with a bisphosphonate within the previous 12 months were excluded.
A total of 4 courses of FEC100 were administered every 3 weeks followed by weekly paclitaxel for 12 courses. ZOL 4mg was administered every 3–4 weeks a total of 7 times.
Patients were randomized 1:1 to chemotherapy + ZOL group or chemotherapy alone group, according to the presence or absence of lymph node metastasis, estrogen receptor (ER) status, and their menopausal status.
The primary endpoint was the rate of pCR defined as absence of invasive disease in the breast at surgery. Secondary endpoints were tumor response rate (RECIST ver1.0), the breast-conserving surgery ratio, and disease-free survival (DFS).
We calculated the sample size on the basis of a pCR rate of 18% in the chemotherapy alone group and 35% in the chemotherapy + ZOL group, at 5% significance level based on the one-sided chi-square test with the statistical power of 80%, and as a result we targeted a patient sample size of 180 patients.
Results: 188 patients were recruited between March 2010 and April 2012. Results of the primary analysis of efficacy and safety will be presented.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD07-05.