bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preventive effects of the EGFr inhibitor erlotinib in ER+ methylnitrosourea (MNU) induced and in ER- MMTV/Neu/P53KO mammary cancer models.
Authors: Grubbs CJ , Iwata KK , Buck E , Juliana M , Lubet RA 
Published: December 2010

Abstract
Abstract #1112
The preventive/therapeutic efficacies of Erlotinib in both ER+ and ER- models of breast cancer in rats and mice, respectively, were evaluated. For the ER+ model, female Sprague-Dawley rats were administered MNU at 50 days of age. Beginning five days later, Erlotinib was administered 7x/week for the remainder of the study. Daily administration of Erlotinib in a prevention setting at 4 and 1.33 mg/kg BW/day reduced tumor multiplicity by 72 and 35%, respectively; doses &gt;6 mg/kg BW/day decreased cancers by &gt;90%. When rats with palpable mammary cancers were treated for six weeks with 4 mg/kg BW/day of Erlotinib, most of the tumors showed highly significantly regressions. Similarly, when rats bearing palpable mammary cancers were treated with Erlotinib for 5 days (3 or 1 mg/kg BW/day), large decreases in tumor cell proliferation and alterations in expression of phosphorylated EGFr, AKT, ERK and SHC were observed. In additional studies, the preventive effect of Erlotinib in a MMTV/Neu/P53KO bitransgenic model was examined. These mice develop ER- cancers which overexpress Neu and have an alteration in P53. These changes are characteristic of ER- human breast cancers. An initial experiment showed that Erlotinib (50 mg/Kg BW/day) was also effective as a preventive agent in this model. Effects of this agent on proliferation and altered expression of phosphorylated EGFr, AKT, ERK and SHC are in progress. Our results showing efficacy of the EGFr inhibitor Erlotinib in ER+ mammary cancers are in agreement with a clinical study of early stage human ER+ breast cancer showing that the EGFr inhibitor Gefitinib is highly effective in ER+/EGFr+ tumors (Polychronis, et al., Lancet Oncolo.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1112.
Expression profile of CYP19 in human breast cancer cell lines treated with indole-3-carbinol, 3,3'-diindolylmethane, and sulforaphane.
Authors: Licznerska BE , Matuszak I , Baer-Dubowska W 
Published: December 2010

Abstract
Abstract #1113
Breast cancer is the most frequently diagnosed cancer in Western women. Most cases (up to 75%) are estrogen-dependent. The estrogen-independent cases are more invasive, more difficult to treat, and they are connected with worse prognosis. The biologically active estrogens important in the proliferation of breast cancer are produced from inactive precursors by the action of aromatase encoded by CYP19 gene. Conventional treatment (e.i. hormonal therapy) is expensive and for advanced cancer ultimately unsuccessful. That is why early diagnosis and prevention of this disease is urgently needed. A new hope is brought by chemoprevention – the concept of early intervention by usage of different agents inhibiting the development of invasive cancer. Recent epidemiological migrant studies showed that consumption of raw or short cooked cabbage and sauerkraut is connected with significant reduction of breast cancer incidences. Indole-3-carbinol (I3C), 3,3'-diindolylmethane (DIM) – a major in vivo acid-catalyzed condensation product of I3C, and sulforaphane (SUL) are examples of numerous active chemicals in cabbage.&#x2028; The aim of the present study was to investigate the effect of I3C, DIM and SUL on the profile of CYP19 expression in human breast cancer estrogen-dependent MCF-7 cell line. Cells were treated with these compounds at the concentrations relevant to those observed in human plasma. The total RNA extraction from cell cultures after 144 hours of incubation with different substances concentrations and reverse transcriptase reaction preceded the cDNA synthesis. The screening of cDNA from aromatase mRNA was performed using real-time PCR assay. The results showed that I3C in the dose of 30 μM reduced the expression of CYP19 in MCF-7 cell line. In contrast, higher dose of I3C (50 μM) induced its expression. The latter results confirmed the observations of the other authors indicating reciprocal I3C effect on carcinogenesis. SUL in the doses of 5μM and 20μM diminished the level of CYP19 mRNA. Similar trend was observed after treatment with 5 μM and 10 μM of DIM. Since the down-regulation of CYP19 gene causes the reduction in estrogens synthesis the usage of I3C, DIM, and/or SUL could be well-founded as preventive agents against breast carcinoma development. Further investigation on estrogen-independent MDA-MB-231 cell line which is under way are necessary to compare the possible application of I3C, DIM, and SUL as a chemopreventive agents depending on the hormonal character of the tumour.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1113.
Treatment of early breast cancer in women over 65: what is important? Retrospective trial.
Authors: Kim K , Jung Y , Hur L , Kim S 
Published: December 2010

Abstract
Abstract #1125
Introduction-Background-Objective&#x2028; There are some demonstrations for the under-treatment of elderly (age 65 or older) women with early breast cancer. However, a few reports are available for overall survival as well as treatment patterns. To characterize treatment patterns and to determine the impact of under-treatment of early breast cancer in the elderly population compared to younger population.&#x2028; Methods&#x2028; We analyzed data of 4,990 early (stage I, II) breast cancer patients aged ≥ 50 years old postmenopausal women, registered in the Korean Breast Cancer Society Registration Program (KBCSRP) between 1992 and 2001 retrospectively. We compared elderly group (age 65 or older) with younger group (age 50 or older, and under age 65) in cancer stage, hormonal receptor status, p53 status, HER-2 status, breast conservation rate, radiation therapy omission rate after breast conservation surgery, chemotherapy rate, hormonal therapy rate and overall survival.&#x2028; Results&#x2028; 942(19%) patients were in the elderly group and 4,048(81%) patients were in the younger group. We followed up to 2004 and median follow up period were 5.7 years. There were no differences in cancer stage, HER-2 status, and hormonal therapy rate.&#x2028; In elderly group, tumor had two better prognostic factors: more hormonal receptor positivity (63.3% vs. 59.3%; p=0.001) and less p53 positivity (37.3% vs. 49.5%: p&lt;0.001). Overall survival, however, was lower than younger group: 83% vs. 91% in 5 year survival rate, 68% vs. 81% in 10 year survival rate, respectively. Elderly group had less breast conservation rate (16.4% vs. 20.4%; p&lt;0.001), more radiation omission rate after breast conservation surgery (59.8% vs. 15.3%; p&lt;0.001) and less chemotherapy rate (43% vs. 70.6%; p&lt;0.001). Using log-rank analysis, overall survival was affected by under-treatment of disease: women who underwent breast conservation surgery without radiation therapy experienced a significant decreased survival compared to women with radiation therapy (68% vs. 84% in 10 year survival rate; p&lt;0.001). Total mastectomy was not superior to breast conservation surgery plus radiation therapy (p=0.2856). Women who underwent chemotherapy, however, revealed no survival gains, but women with hormonal therapy showed superior survival rate (p=0.0019).&#x2028; Conclusions&#x2028; Our data revealed that elderly patients had better prognostic tumor characteristics, but lower survival rate. Deviated under-treatment patterns in elderly early breast cancer patient could be dangerous choice to patients, therefore, radiation therapy after breast conservation surgery should not be omitted and hormonal therapy should be recommended especially.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1125.
Phase III randomized adjuvant study of tamoxifen alone versus sequential tamoxifen and anastrozole in postmenopausal women with hormone-responsive breast cancer: N-SAS BC03 study.
Authors: Aihara T , Takatsuka Y , Osumi S , Aogi K , Hozumi Y , Imoto S , Mukai H , Iwata H , Watanabe T , Shimizu C , Nakagami K , Tamura M , Ito T , Masuda N , Ogino N , Hisamatsu K , Mitsuyama S , Abe H , Yamaguchi T , Ohashi Y 
Published: December 2010

Abstract
Abstract #1138
Background. Clinical trials conducted in Western countries have shown that improved disease-free survival (DFS) is associated with the use of aromatase inhibitors instead of tamoxifen in postmenopausal women with early breast cancer. Pharmacogenetic differences in drug metabolizing genes may cause ethnic differences in the response or tolerability to aromatase inhibitors, as well as tamoxifen. In fact, improved DFS by extending the use of letrozole after tamoxifen for 5 years has not been confirmed in women from minority groups (Ann Oncol. 2006 17(11):1637-43). Therefore, assessment of the efficacy of aromatase inhibitors in non-white women is warranted. We report the results of switching adjuvant therapy from tamoxifen to anastrozole in postmenopausal Japanese women with breast cancer enrolled in an open-label, randomized clinical trial (N-SAS BC03 study). Patients and Methods. From November 2002 to December 2005, 706 postmenopausal women with hormone-receptor-positive breast cancer who were receiving adjuvant therapy with tamoxifen for 1 to 4 years were randomly assigned to either continue tamoxifen or to switch to anastrozole; the total duration of treatment was 5 years. Primary endpoints were DFS and adverse events. Secondary endpoints included relapse-free survival (RFS), overall survival (OS) and QOL. Results. After a median follow-up of 42 months (range, 3.2-60), there were 26 events in the anastrozole group as compared with 37 in the tamoxifen group related to DFS, and 15 events in the anastrozole group as compared with 28 in the tamoxifen group related to RFS. The unadjusted hazard ratio was 0.69 (95 percent confidence interval, 0.42 to 1.14; P=0.06 by the log-rank test) for DFS and 0.52 (95 percent confidence interval, 0.28 to 0.98; P=0.02 by the log-rank test) for RFS, both in favor of anastrozole. There was no difference in OS (p=0.49). Conclusion. Switching from tamoxifen to anastrozole was confirmed to be associated with a lower disease recurrence rate than continuing tamoxifen in postmenopausal Japanese women with breast cancer.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1138.
Effects of switching aromatase inhibitors on arthralgia: the ATOLL study.
Authors: Briot K , Bastit L , Rotarsky M , Spaeth D , Tubiana M , Mauresan Kloos I , Bourdeix I , Roux C 
Published: December 2010

Abstract
Abstract #1142
Background: Aromatase inhibitors (AIs) are standard adjuvant therapy in postmenopausal women (PMW) with hormone receptor-positive breast cancer (HR+BC). The estrogen-deficient environment induced by AIs may predispose women to increased bone loss and arthralgia. Switching from one AI to another has been shown to improve arthralgia. However, clinical trial data documenting the course of joint pain symptoms in switching studies has been sparse. The Articular Tolerance of Letrozole (ATOLL) study evaluates the tolerability of letrozole (L) in patients who were switched from anastrozole (A) due to severe joint pain.&#x2028; Objectives: This study included PMW with HR+BC who experienced severe joint pain with A requiring discontinuation and then switched to L. The aim of the study was to (i) determine the incidence of L discontinuation due to joint pain (ii) identify predictive factors for L tolerance.&#x2028; Methods: Only PMW with HR+ BCwho experienced severe joint pain on A requiring discontinuation were eligible for this 6-month prospective open-label, multi-centre trial. Treatment with L was initiated following a 1 month washout period. Pain assessment was done by a oncologist just prior to L initiation and after six months of follow up. Outcomes were based on patient reports of joint pain after initiating L. A central review was done by a rheumatologist. Statistical evaluations were determined on a 95% CI, and correlations were performed using a Cox model.&#x2028; Results: 179 PMW with HR+ breast cancer (mean age 61.3 ± 8.4) were eligible. The mean duration of A treatment prior to discontinuation was 14.6 ± 10.59 months with 126 (73.7%) on A for more than 6 months. At the end of the 6 month follow-up, 128 patients (71.5%) remained on L and continued by choice while 51(28.5%) patients discontinued L due to worsening of joint pain;73.5% patients discontinued due to arthralgia and 21% due to muscle pain . Hands, knees and spine were the most commonly affected joints. There was no association between L discontinuation with age, duration of menopause, socio-demographic status or previous joint disorders including osteoarthritis. The predictor of L discontinuation was significant only for the duration of the previous A treatment (p=0.04).&#x2028; Conclusion: These data suggest switching from anastrozole to letrozole may help to maintain the benefit of AI therapy in patients who complain with severe joint pain and support the reported findings of Renshaw et al that more than 50% of women obtained relief of joint pain by switching from one AI to another. Symptomatic arthralgia due to prolonged use of A reduced the usefulness of switching to L in this patient cohort, therefore, switching from one AI to the other at the onset of symptoms may help to maintain the benefit of AI therapy in patients who complain of severe joint pain.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1142.
A randomised study of the effects of anastrozole (A), letrozole (L) and exemestane (E) on bone turnover.
Authors: McCaig FM , Renshaw L , Williams L , Young O , Murray J , Macaskill EJ , McHugh M , Hannon R , Dixon J 
Published: December 2010

Abstract
Abstract #1145
Background:&#x2028; Aromatase inhibitors (AIs) reduce circulating oestrogen which increases bone turnover. L decreases circulating oestrogen levels to a greater degree than A. This study compares the effects of the non-steroidal aromatase inhibitors, A and L and the steroidal inactivator, E on bone turnover.&#x2028; Patients and Methods:&#x2028; This was an open, randomized pharmacodynamic study. Bone turnover markers were measured in 162 postmenopausal women with invasive ER +ve breast cancer. As part of their adjuvant hormone therapy, patients were randomized to receive either:&#x2028; 16 weeks of A, 16 weeks of L or 16 weeks of E&#x2028; Fasting blood and urine samples were collected at entry and after 12 and 16 weeks of each drug. Bone remodelling releases breakdown products of type 1 collagen including the terminal peptide fragments N-terminal telopeptides (NTx) and C-terminal telopeptides (CTx). An increase in these indicates bone resorption. Increases in type 1 pro-collagen peptides (N-terminal – PINP) and bone specific alkaline phosphatase (ALP) indicate bone formation. These were measured as was parathyroid hormone (PTH) which is an indirect measure of overall bone turnover.&#x2028; Results:&#x2028; A vs E vs L&#x2028; A, E and L significantly increased the bone turnover markers - PINP, CTX and bone ALP.&#x2028; E showed a greater change in bone turnover but there were no significant differences between the drugs.&#x2028; &#x2028; &#x2028; &#x2028; E resulted in a greater increase in PINP and uNTX compared to the non-steroidal AIs however these were of borderline significance.&#x2028; PINP, CTX and bone ALP all have significantly higher than zero percentage changes, regardless of drug or drug type.&#x2028; Conclusions:&#x2028; AIs cause a significant increase in both bone breakdown and bone formation.&#x2028; There is no evidence to suggest E has less effects on bone turnover than A or L.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1145.
Endocrine effects of adjuvant letrozole versus tamoxifen in hormone responsive postmenopausal early breast cancer patients: results from the HOBOE randomized trial.
Authors: Morabito A , Rossi E , Di Rella F , Esposito G , Gravina A , Labonia V , Landi G , Nuzzo F , Pacilio C , De Maio E , Piccirillo M , De Feo G , D'Aiuto G , Botti G , Gallo C , Perrone F , de Matteis A 
Published: December 2010

Abstract
Abstract #1150
Purpose. We compared the endocrine effects of 6 and 12 months of adjuvant letrozole versus tamoxifen in postmenopausal patients with hormone responsive early breast cancer, within an ongoing phase 3 trial (HOrmonal adjuvant treatment BOne Effects – HOBOE, ClinicalTrial.gov id: NCT00412022).&#x2028; Patients and Methods. Patients were randomised to receive tamoxifen or letrozole ± zoledronate. Serum values of 17-b-estradiol, FSH, LH, testosterone, dehydroepiandrosterone-solphate, progesterone, and cortisol were measured at baseline, after 6 and 12 months of treatment. For each hormone, baseline, 6 and 12-month values were compared between treatment groups, by the exact Wilcoxon-Mann-Whitney test.&#x2028; Results. At December 31, 2006, 157 postmenopausal patients had been enrolled into the study; baseline data were available for 139 patients (88.5%), 43 assigned to tamoxifen and 96 assigned to letrozole. Median age was 61 and 62 years in the two groups, respectively. Baseline values were similar between the two groups for all hormones. At 6 and 12 months, levels of 17-b-estradiol were significantly lower with letrozole as compared with tamoxifen (p=0.0003 and p&lt;0.0001, respectively). Patients treated with letrozole also showed higher levels of progesterone and testosterone at 6 (p=0.001 and p=0.01, respectively) and 12 months (p=0.004 and p=0.02, respectively) than those treated with tamoxifen. FSH and LH were lower (all p&lt;0.0001 for both hormones), while cortisol was higher (p=0.003 at 6 and 0.001 at 12 months) with tamoxifen than with letrozole.&#x2028; Conclusion. To our knowledge, this is the first study reporting on endocrine effects of letrozole as adjuvant treatment of postmenopausal early breast cancer and allowing a prospective comparison with tamoxifen. Adjuvant letrozole and tamoxifen result in significantly distinct endocrine effects. Such differences can explain the higher efficacy of letrozole as compared to tamoxifen. Long-term impact needs to be studied.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1150.
BIG 1-98: A randomized double-blind phase III study evaluating letrozole and tamoxifen given in sequence as adjuvant endocrine therapy for postmenopausal women with receptor-positive breast cancer.
Authors: Mouridsen HT , Giobbie-Hurder A , Mauriac L , Paridaens R , Colleoni M , Thuerlimann B , Forbes JF , Gelber RD , Wardley A , Smith I , Price KN , Coates A , Goldhirsch A ,   BIG I-98 Collaborative and the International Breast Cancer Study Group
Published: December 2010

Abstract
Abstract #13
Background: BIG 1-98 compares letrozole (Let), tamoxifen (Tam) and sequences of Let and Tam as adjuvant endocrine therapy for postmenopausal women with receptor-positive breast cancer. Initial results (published in 2005) demonstrated the superiority of Let over Tam in significantly prolonging disease-free survival (DFS) and reducing the risk of relapse in distant sites. Following these results, investigators were informed of the treatment allocation for patients randomized to Tam alone, and about one third of these patients opted to receive Let. The three Let-containing treatments remained blinded. We now evaluate Let and Tam given in sequence compared with Let alone and update the comparison of Let alone and Tam alone.&#x2028; Methods: 6182 patients were randomized to the 4-arm option (entry Sep99-May03) [Tam x 5 years (Tam), Let x 5 (Let), Tam x 2→Let x 3 (Tam→Let), or Let x 2→Tam x 3 (Let→Tam)]. Another 1828 patients were randomized to the 2-arm option (Tam vs. Let; entry Mar98-Mar00). The primary endpoint was DFS (time from randomization to first occurrence of invasive breast cancer recurrence, invasive contralateral breast cancer, second non-breast malignancy, or death from any cause). The presentation will focus on the clinically-relevant comparisons evaluating Tam→Let vs. Let and Let→Tam vs. Let, assessed from the time of randomization. Acknowledging multiple comparisons, the hazard ratios are presented with 99% confidence intervals (CIs).&#x2028; Results: The median follow-up time is 71 months. Hazard ratios comparing treatments from time of initial randomization in terms of DFS, overall survival, and time to distant recurrence are displayed below.&#x2028; &#x2028; With this long term follow-up, adverse events for Let and Tam are consistent with the known safety profile of both agents.&#x2028; A protocol-specified update of the previously-reported comparison of Let x 5 vs. Tam x 5 (i.e., the monotherapy arms, including patients in both the 2-arm and 4-arm options; N=4922) suggests improved survival for patients treated with Let (HR=0.87, 95% CI=0.75-1.02, p=0.08, 76 months median follow-up). In this comparison, about a quarter of the patients in the Tam arm crossed over to Let after 3-5 years of Tam.&#x2028; Conclusion: The sequential treatments did not improve DFS compared with Let alone. Trends support initial use of Let in patients at higher risk of relapse. Patients commenced on Let can be switched to Tam if required. Updated results of the monotherapy comparison suggest superior overall survival with Let compared with Tam.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 13.
Tamoxifen and anastrozole as a sequencing strategy in postmenopausal women with hormone-responsive early breast cancer: updated data from the Austrian breast and colorectal cancer study group trial 8.
Authors: Jakesz R , Gnant M , Griel R , Tausch C , Samonigg H , Kwasny W , Kubista E , Stierer M , Luschin G , Rüecklinger E , Mittlböck M 
Published: December 2010

Abstract
Abstract #14
Background: Historically, standard endocrine treatment for postmenopausal women with hormone-sensitive early breast cancer (EBC) was 5 years' tamoxifen. However, the inclusion of an aromatase inhibitor (AI) is now considered standard practice. There is increasing evidence that whether as initial adjuvant treatment or as a switch treatment following 2-3 years of tamoxifen therapy, Ais improve patients' outcomes compared with 5 years' tamoxifen monotherapy.&#x2028; To date, there is limited evidence comparing a prospective sequencing strategy of 2 years of tamoxifen followed by 3 years of an AI compared with 5 years' tamoxifen. Previously presented data from ABCSG Trial 8 (SABCS 2005), at a median follow-up of 55 months, revealed a 24% reduction in the risk of recurrence in favor of a sequencing strategy compared with 5 years' tamoxifen (hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.56-1.02), although the difference was not statistically significant (p=0.07). Here we present updated data from ABCSG Trial 8.&#x2028; Methods: Postmenopausal women with histologically verified G1 or G2, locally radically treated invasive or minimally invasive hormone receptor-positive breast cancer were eligible for inclusion. Newly diagnosed patients were randomized to receive 5 years' tamoxifen therapy or 2 years' tamoxifen followed by anastrozole for 3 years. The primary endpoint was event-free survival, including locoregional and distant metastatic recurrences and new contralateral breast cancers.&#x2028; Results: This final analysis will report the data cut-off point, the number of eligible patients, and the median follow-up period of the trial, which will exceed 5 years. The incidence of first events, local recurrences, distant metastases, and contralateral breast cancers for the two treatment arms of the study will be presented. The effect of treatment on the trial endpoint will be analyzed using a Cox proportional hazards model and data will be presented as estimated HRs with two-sided 95% CIs and p-values.&#x2028; Conclusions: The updated analyses of ABCSG Trial 8 will provide evidence regarding 2 years' treatment with tamoxifen followed by 3 years' anastrozole in comparison to 5 years' tamoxifen for postmenopausal women with newly diagnosed hormone-sensitive EBC.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 14.