bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential economic impact of the 21-gene recurrence score in Brazil.
Authors: Bacchi CE , Saad ED , Carvalho FM , Ojopi EB , Prisco FE 
Published: December 2010

Abstract
Abstract #6102
Objective: The 21-gene recurrence score (RS) may be useful for decisions regarding the use of chemotherapy (CT) in patients with lymph-node-negative (LNN), estrogen-receptor (ER)+ early breast cancer (BC). We investigated the potential impact of using RS in private practice in Brazil, from the perspective of third-party payers, in terms of main direct medical expenses.&#x2028; Methods: We conducted a web-based survey with 30 (of a total of ∼700) Brazilian medical oncologists, who were stratified by State according to the proportion of patients with BC and private insurance. Such physicians represented States and cities in which approximately 80% of new BC cases are diagnosed each year. The questionnaire evaluated the treatment of first choice for patients with LNN, ER+ BC, regardless of menopausal status. Interviewees were initially invited by telephone and were not aware of the objective of the study. The responses allowed a quantitative assessment of the patterns of care regarding CT regimen according to disease stage (T1b, T1c, T 2-4 cm, T &gt; 4 cm), type of premedication, use of G-CSF and in-hospital treatment for febrile neutropenia (rates taken from the literature). Medication costs were calculated using the manufacturer's recommended prices, and the cost for RS testing, which is currently available in Brazil, was set at BR$ 3,900.00 (US$ 2,294.00). Other direct medical expenses, indirect medical costs, and non-medical costs were not considered. We estimated costs for two hypothetic cohorts of patients (without and with RS), whose stage distribution and RS results followed those reported by Paik et al (NEJM 2004). The model assumed that patients with access to RS testing would receive CT if their RS was intermediate or high, whereas patients with a low RS would receive no CT.&#x2028; Results: For a hypothetic cohort of 100 patients with no access to RS testing, the survey showed that 84 patients would receive CT (of note, 43% of patients with T1b tumors and adverse features would not receive CT). Reclassifying patient eligibility to CT according to RS would bring this number to 49. For a hypothetic cohort of 100 patients, BR$ 134,958.00 (∼US$ 79,400.00) would be saved in main direct medical expenses.&#x2028; &#x2028; Conclusion: Considering the current price for the exam, our economic analysis suggests that RS testing is cost-saving in Brazil, from the perspective of third-party payers. Prospective studies are awaited for validating CT decisions based on the RS.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6102.
Carmustine-methotrexate combination in breast cancer patients presenting with brain metastases.
Authors: Jacot W , Gerlotto-Borne M , Thezenas S , Pouderoux S , About M , Romieu G 
Published: December 2010

Abstract
Abstract #6119
Purpose: There is currently no standard chemotherapy regimen for breast cancer (BC) patients presenting with brain metastases (BM). Since 1999, in our institution, these patients are treated with an association of carmustine (BCNU) and methotrexate (MTX). We report here the efficacy and safety profile of this association. Patients and methods: In this study, BC patients presenting with BM were treated by an association of BCNU 100 mg/m² on day 1 and MTX 600 mg/m² on day 1 and 15 of a 28 days cycle. Treatment was continued until progression or unacceptable toxicity. In order to evaluate this combination, we analyzed activity by recording tumor response rates, progression-free survival (PFS) and overall survival (OS), treatment compliance by analyzing Relative Dose Intensity (RDI) and safety by analyzing clinical and biological toxicities using NCI CTCAE v3.0. Results: Fifty patients were treated between 1999 and 2007, with a median age of 52 years (range 26-77 years). Median time between diagnosis of BC and BM was 37 months (0-180). One patient had synchronous BM. No tumor was recorded to be Scarf, Bloom and Richardson grade I, 40% were hormonal receptor negative and 50% of the 36 tumors analyzed for HER-2 amplification were positive. 94% of the patients presented with concomitant extra-cerebral disease, mainly bone (76%), liver (46%), lung (42%) and lymph node (26%) metastases. The number of previous chemotherapy regimens in the metastatic setting was 2 (1-5). The median number of administered cycles of BCNU-MTX was 3 (1-20). 30% of the patients received up to 6 chemotherapy cycles, with 20% patients continuing the treatment after 6 cycles. There were 11 objective responses (23% [IC95% 12-37]) among 48 evaluable patients, with an additional 29% disease stabilization, for a total 52% of patients with clinical benefit. Median PFS and OS were 4.2 (95%CI: 2.8-5.3) and 6.9 (4.2-10.7) months respectively, with a one-year OS rate of 32% (20-46). There were 2 presumed treatment-related deaths. The median RDI for BCNU and MTX were 0.98 (0.31-1.1) and 0.96 (0.57-1.66) respectively. Treatment was well tolerated, with the most common grade 3-4 toxicities per patients as follow (%pts): anemia (8.4), neutropenia (40.4), thrombocytopenia (21.2), and grade 3 fatigue (10.6). One patient developed febrile neutropenia. Poor prognosis was associated with a poor performance status in a univariate analysis of OS.Conclusion: In this population of heavily pretreated patients affected by BM from BC, the combination of BCNU-MTX appears to be an effective and well tolerated combination in good performance status BC patients presenting with BM.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6119.
Oral combination chemotherapy with capecitabine and cyclophosphamide in patients with metastatic breast cancer: phase II study.
Authors: Tanaka M , Tamura K , Anan K , Ohno S , Nishimura R , Yamamoto Y , Masuda N , Mitsuyama S 
Published: December 2010

Abstract
Abstract #6120
Background : Capecitabine and cyclophosphamide(XC) are shown to have a synergistic effect in the preclinical study and can be given orally with non-overlapping toxicities. Phase I study of XC was conducted for metastatic breast cancer patients and the recommended dose was 1657/mg/m2/day of X and 65mg/m2/day of C, respectively, which were to be given daily for 2 weeks at every 3-week schedule. We conducted phase II study with this regimen.&#x2028; Patients and methods: Women with advanced or metastatic breast cancer who had been treated previously with anthracyclines but not with taxanes, were entered into this trial. Other eligibility criteria included an age from 20 to 74 years, ECOG performance status 0-2, presence of measurable lesions according to the RECIST criteria, HER2-negative tumors, and acceptable major organ functions. One course of XC consisted of the above recommended dose and schedule, and at least 6 courses were to be given unless progression of the disease or unacceptable toxicities occurred. The primary endpoint was response rate and the secondary endpoints were progression free survival (PFS), overall survival (OS) and adverse events. The study was started in July 2005 and ended in December 2007.&#x2028; Results: Forty-eight patients were registered. The median age was 57 (range: 32 to 72). Thirty-three patients were postmenopausal. Estrogen and progesterone receptor was positive in 30 and 23 patients, negative in 14 and 19, and unknown in 4 and 6 patients, respectively. Three patients never received XC, and 2 patients were withdrawn from the study due to nausea and vomiting during the first course. Two patients were not evaluable for tumor response. Among 43 evaluable patients, there was complete response in 2 patients, partial response in 14, stable disease in 8, and progression of the disease in 19. Thus, an overall response rate was 87%. The response rate of metastatic lesions in each organ was 50% in lungs (6 patients), 65% in liver (17), 80% in lymph nodes (15), and 1.4% in skin (7), respectively. The median PFS and OS was 146 (85 to 942+) days and 672 days with a median follow-up time of 311 (97-1045+) days, respectively. Grade 3 toxicity was encountered for neutropenia with no fever in 5, anorexia in 2, and nausea/vomiting and diarrhea in 1 of each patient. Grade 1 and 2 hand-foot syndrome was experienced in 12 and 2 patients, respectively. One patient with liver metastasis showed grade 3 anemia, thrombocytopenia and elevated serum transaminase levels.&#x2028; Conclusion: Oral XC combination (1657/mg/m2/day and 65mg/m2/day for 2 weeks at every 3-week schedule) is effective to women with advanced or metastatic breast cancer with acceptable toxicities.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6120.
High dose estrogen as a salvage hormonal strategy for highly refractory metastatic breast cancer (MBC): “back to the future.”.
Authors: Mahtani RL , Stein A , Vogel CL 
Published: December 2010

Abstract
Abstract #6129
High dose estrogens are an efficacious but widely ignored treatment option for patients with MBC. This is due in part to the introduction of tamoxifen, which was shown to be equivalent in efficacy with fewer side effects in the 1970's. After local Institutional Review Board approval we identified 26 patients with MBC treated in our practice with either diethylstilbestrol (15mg/day) or estradiol, generally, at a dosage of 30mg daily. One patient remains too early to evaluate. The median age at initial diagnosis was 46 and median age for patients at the start of high dose estrogen therapy was 59. All but 2 patients had confirmed hormone receptor positive tumors (one with a very long disease free interval and the other, prior response to hormonal therapy). Two of 26 patients were HER-2neu + by FISH analysis. The median # of sites of disease was 2 (range 1-3) and 50% had dominant visceral disease. Patients had received a median of 3 prior chemotherapy regimens (range 0-7), and 4 prior hormonal regimens (range 1-7), for a median of 7 prior systemic therapies (range 0-12). The median distant disease free interval (DFI) was 62 months (range 0 to 264 months). The median time from recurrence to initiation of estrogen therapy was 57 months (range 1 to 132 months). Six of 25 (24%) currently evaluable patients had objective anti-tumor responses, with one having a complete response in liver of 22 months. In addition, 4 of 25 patients (16%) with less clearly measurable disease had prolonged stable disease for ≥ 6months (7, 9, 13, and 14months, respectively). Clinical benefit (defined as CR, PR, and prolonged SD ≥6months) was 40%, with median duration of 9 months (mean of 12). Two patients are in continuing remission at 7 and 14months, respectively. Toxicities included vaginal bleeding in 7 of 25 (6 grade 1 and 1 grade 2), nausea in 4, and fluid retention in 8 (7 grade 1 and 1 grade 2). The patient with grade 2 fluid retention responded to a dose reduction to 6mg daily. Only 3 of 25 of patients discontinued estrogen therapy due to toxicity (1 vaginal bleeding, 1 refused to continue, and 1 nausea). In addition, one of the 3 patients that discontinued due to toxicity had a prolonged estrogen withdrawal response of 12months duration after 9 months of stable disease. Conclusion: Almost all patients with hormone receptor (+) MBC eventually develop resistance to endocrine agents. These data confirm the efficacy of high dose estrogens as yet another option for heavily-treated patients in whom further endocrine manipulation might still be appropriate.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6129.
Fertility and pregnancy in patients below the age of 35 following chemotherapy for breast cancer.
Authors: Katz D , Hamburger T , Divinsky L , Temper M , Ospovat I , Salah A , Galinsky D , Peretz T 
Published: December 2010

Abstract
Abstract #6148
Background&#x2028; Counseling young breast cancer patients regarding the chances of conception following chemotherapy is a subject of great importance. Previous studies have reported a 50-70% rate of amenorrhea following standard breast cancer chemotherapy and very low rates of pregnancy. However a uniform definition of infertility is lacking and as a result many studies reported results observed in pre-menopausal women as a whole without specific analysis and separation according to age. In this retrospective, single institution study, we examined resumption of menses and pregnancy rates in young breast cancer patients who had received chemotherapy.&#x2028; Methods&#x2028; We identified 193 breast cancer patients aged 35 years or younger diagnosed at a single institution between 1996 and 2004. All patients who were treated with adjuvant chemotherapy and had completed at least 1 year of follow-up without evidence of recurrence were included in the study.&#x2028; Results&#x2028; Forty seven patients met the eligibility criteria. The mean time of follow-up was 69 months (range, 12-124 mos.). The mean age at diagnosis was 30 years (range, 19-34 yrs). Chemotherapy consisted of Adriamycin based protocols in 29 cases and CMF (Cyclophosphamide, Methotrexate, 5-Fluorouracil) in 18 cases. GnRH agonists were administered to 28 (61%) of patients for at least two years. All patients had regular menses prior to the initiation of chemotherapy. Three patients continued to receive regular injections with a GnRH agonist beyond two years, one patient underwent oophorectomy, two patients developed amenorrhea whilst 35 patients (35/37 95%) resumed menses subsequent to chemotherapy. Information regarding menstruation was lacking for six patients. Sixteen patients (16/37 43%) gave birth to at least one child after menses resumed at a mean age of 35 years (range, 28-41yrs).&#x2028; Discussion&#x2028; Standard chemotherapy protocols in breast cancer patients under the age of 35 do not preclude fertility preservation and pregnancy. However, not all young breast cancer survivors wish to become pregnant following treatment and therefore the actual rate of fertility is in fact higher than those recorded. Further prospective studies which incorporate documentation regarding patient's desire for future pregnancies need to be undertaken in order to better advise young patients with respect to their individual chances of conceiving following chemotherapy.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6148.
Breast cancer after stopping estrogen plus progestin in postmenopausal women in the women's health initiative.
Authors: Chlebowski RT , Kuller L , Anderson G , Mason J , Schenken R , Rajkovic A , Stefanick M , Sarto G , Ravdin P , Prentice R 
Published: December 2010

Abstract
Abstract #64
Background&#x2028; Following the Women's Health Initiative (WHI) estrogen plus progestin (E+P) trial report (JAMA 2002;288:321), menopausal hormone therapy use decreased dramatically in the United States. Subsequently, breast cancer incidence also dropped substantially, suggesting possible causality (NEJM 2007;16:1680); however, the etiology remains controversial.&#x2028; Methods&#x2028; To define effects of stopping E+P on breast cancer incidence more precisely, additional analyses were conducted in the WHI randomized trial of daily conjugated equine estrogens (CEE, 0.625 mg) plus medroxyprogesterone acetate (MPA, 2.5 mg) versus placebo. Furthermore, temporal trends for breast cancer diagnoses in the WHI observational study cohort were examined. Breast cancer risk factors, mammography utilization and calendar time-specific breast cancer incidence were assessed relative to E+P use.&#x2028; Results: The time-specific linear hazard ratio (HR) curves examining E+P influence on breast cancer in the E+P clinical trial (CT), and in the observational study (OS, the later adjusted for E+P use during follow-up) are attached.&#x2028; &#x2028; &#x2028; &#x2028; In the CT, breast cancer incidence, initially lower in the E+P group, increased with longer duration use but decreased postintervention despite closely comparable mammogram frequency between randomization groups. In the OS, breast cancer incidence was about two-fold higher in E+P users vs non-users (likely reflecting longer duration exposure) but decreased rapidly following year-to-year reductions in E+P use, while differences in mammogram frequency between E+P users and non-users were unchanged.&#x2028; Conclusion: These findings suggest that cessation of E+P use is associated with a rapid reduction in breast cancer incidence which is not explained by mammography utilization change and support the hypothesis that the recent reduction in breast cancer incidence seen in certain age groups is predominantly related to a decrease in combined menopausal therapy use.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 64.
A meta-analysis of phase III trials evaluating the predictive value of HER2 and topoisomerase II alpha in early breast cancer patients treated with CMF or anthracycline-based adjuvant therapy.
Authors: Di Leo A , Isola J , Piette F , Ejlertsen B , Pritchard KI , Bartlett JM , Desmedt C , Larsimont D , Tanner M , Mouridsen H , O'Malley FP , Twelves C , Cardoso F , Poole CJ , Piccart MJ , Buyse ME 
Published: December 2010

Abstract
Abstract #705
Background: Retrospective studies have suggested that HER2 and topoisomerase II α (TOP2A) might predict sensitivity to anthracyclines (A)&#x2028; Methods: Four phase III trials comparing A with CMF in early breast cancer (EBC) patients (pts), and with available primary tumor samples, were identified. HER2 and TOP2A genes were evaluated locally by FISH (amplification if ratio ≥ 2). Data were centralized at the statistical office (IDDI, Belgium). On-site visits were performed to check data quality and laboratory procedures. HER2 and TOP2A local scores were validated by submitting randomly selected samples to a central lab (CL) (University of Tampere – Finland), for a 3 color FISH test (HER2, TOP2A, centromere 17, Abbott Labs, IL, USA). Estrogen (ER), progesterone (PgR) receptors, and grade (G) were evaluated locally (no score validation at the CL).&#x2028; Results: We present the results of the planned interim analysis on 1944 pts. Final results (± 3500 pts) will be presented when tumor sample collection for the UK trial is complete. HER2 local scores were validated at the CL in 137 cases (discordance: 8/137, 5.8%). TOP2A local scores were validated in 123 cases (discordance 38/123, 30.8%). Half of the TOP2A discordant cases were locally deleted-centrally normal or vice versa.&#x2028; &#x2028; A planned exploratory analysis evaluated the TOP2A predictivity in 4 biologically homogeneous groups: highly or moderately hormone sensitive, HER2+ and ER/PgR negative, triple negative (TN). This analysis did not enhance the TOP2A predictivity in any of the 4 groups. In the TN group (294 pts), the DFS HR was 0.77 (0.54-1.09), suggesting that benefit from A might not be confined to HER2+ pts.&#x2028; Conclusions: The interim analysis shows that HER2 and TOP2A have a clinically modest and a statistically borderline predictive value. In triple negative disease A may be superior to CMF.&#x2028; Acknowledgments: Abbott Laboratories, Belgian Federation Against Cancer, Cancer Research UK, Les Amis de l'Institut Bordet, Pfizer, Scottish BC trials group.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 705.
NSABP B-30: definitive analysis of patient outcome from a randomized trial evaluating different schedules and combinations of adjuvant therapy containing doxorubicin, docetaxel and cyclophosphamide in women with operable, node-positive breast cancer.
Authors: Swain SM , Jeong J , Geyer CE , Costantino JP , Pajon ER , Fehrenbacher L , Atkins JN , Polikoff J , Vogel VG , Erban JK , Livingston RB , Perez EA , Mamounas EP , Ganz PA , Land SR , Wolmark N 
Published: December 2010

Abstract
Abstract #75
Background: The primary aims of this study were to determine 1) if a concurrent regimen of therapy containing cyclophosphamide compared to a sequential regimen containing cyclophosphamide would prolong disease-free survival (DFS) and overall survival (OS) and 2) if a regimen without cyclophosphamide was at least as efficacious as the two regimens containing cyclophosphamide. The secondary aims were to compare toxicities among the three regimens and to compare differences in amenorrhea in premenopausal women in each arm and its relationship to outcome.&#x2028; Materials and Methods: 5351 pts with cT1-3, N0-1, M0 were enrolled from 3/1/99 to 3/31/2004. 1783 pts were randomized to Group 1 [doxorubicin (A) 60 mg/m2 and C 600 mg/m2 q 3 weeks (wks) x 4 followed by docetaxel (T) 100 mg/m2 q 3 wks x 4], 1784 pts to Group 2 [A 50 mg/m2 and T 75 mg/m2 q 3 wks x 4], and 1784 to Group 3 [A 50 mg/m2 T 75 mg/m2 and cyclophosphamide (C) 500 mg/m2 q 3 wks x 4]. All patients with ER-positive tumors received hormonal therapy after completing chemotherapy. The protocol specifies that 800 deaths are required for the definitive analysis. This is expected to occur by Fall 2008.&#x2028; Results: Mean time on study is currently 79 months. At entry, 46% of pts were &lt; 49 yrs; 54% were &gt; 50 yrs. 82% were white, 10% black, 4% Hispanic. 66% had 1-3 positive nodes, 26% had 4-9, and 8% had 10+. 75% of pts were ER pos. 49% had lumpectomy, 51% mastectomy, and 24% local/regional radiotherapy. Mean tumor size was 2.5 cm. The presentation will include the first results of DFS, OS, and relevant toxicities from the trial.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 75.