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Adjuvant Ovarian Suppression in Premenopausal Breast Cancer
Prudence A. Francis, M.D., Meredith M. Regan, Sc.D., Gini F. Fleming, M.D., István Láng, M.D., Eva Ciruelos, M.D., Meritxell Bellet, M.D., Hervé R. Bonnefoi, M.D., Miguel A. Climent, M.D., Gian Antonio Da Prada, M.D., Harold J. Burstein, M.D., Ph.D., Silvana Martino, D.O., Nancy E. Davidson, M.D., Charles E. Geyer, Jr., M.D., Barbara A. Walley, M.D., Robert Coleman, M.B., B.S., M.D., Pierre Kerbrat, M.D.,
Stefan Buchholz, M.D., James N. Ingle, M.D., Eric P. Winer, M.D.,
Manuela Rabaglio-Poretti, M.D., Rudolf Maibach, Ph.D., Barbara Ruepp, Pharm.D.,
Anita Giobbie-Hurder, M.S., Karen N. Price, B.S., Marco Colleoni, M.D., Giuseppe Viale, M.D., Alan S. Coates, M.D., Aron Goldhirsch, M.D.,
and Richard D. Gelber, Ph.D., for the SOFT Investigators and the International Breast Cancer Study Group*
The authors’ affiliations are listed in the Appendix. Address reprint requests to Dr. Francis at the Peter MacCallum Can-cer Centre, Locked Bag 1, A’B eckett St., Melbourne, VIC 8006, Australia, or at ibcsgcc@https://www.doczj.com/doc/0414074985.html,.
Drs. Francis and Regan contributed equally to this article.
* A complete list of investigators in the Suppression of Ovarian Function Trial (SOFT) and the International B reast Cancer Study Group is provided in the Supplementary Appendix, available at https://www.doczj.com/doc/0414074985.html,.
This article was published on December 11, 2014, at https://www.doczj.com/doc/0414074985.html,.
N Engl J Med 2015;372:436-46.DOI: 10.1056/NEJMoa1412379
Copyright ? 2014 Massachusetts Medical Society.
ABSTR ACT
BACKGROUND
Suppression of ovarian estrogen production reduces the recurrence of hormone-receptor–positive early breast cancer in premenopausal women, but its value when added to tamoxifen is uncertain.
METHODS
We randomly assigned 3066 premenopausal women, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. The primary analysis tested the hypothesis that tamoxifen plus ovarian suppression would im-prove disease-free survival, as compared with tamoxifen alone. In the primary analysis, 46.7% of the patients had not received chemotherapy previously, and 53.3% had received chemotherapy and remained premenopausal.
RESULTS
After a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6% in the tamoxifen–ovarian suppression group and 84.7% in the tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95% confidence interval [CI], 0.66 to 1.04; P = 0.10). Multivariable allowance for prognostic factors suggested a greater treatment effect with tamoxifen plus ovarian suppression than with tamoxifen alone (hazard ratio, 0.78; 95% CI, 0.62 to 0.98). Most recurrences occurred in patients who had received prior chemotherapy, among whom the rate of freedom from breast cancer at 5 years was 82.5% in the tamoxifen–ovarian suppression group and 78.0% in the tamoxifen group (hazard ratio for recurrence, 0.78; 95% CI, 0.60 to 1.02). At 5 years, the rate of freedom from breast cancer was 85.7% in the exemestane–ovarian suppression group (hazard ratio for recurrence vs. tamoxifen, 0.65; 95% CI, 0.49 to 0.87).
CONCLUSIONS
Adding ovarian suppression to tamoxifen did not provide a significant benefit in the overall study population. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of ovarian suppression improved disease outcomes. Further improve-ment was seen with the use of exemestane plus ovarian suppression. (Funded by Pfizer and others; SOFT https://www.doczj.com/doc/0414074985.html, number, NCT00066690.)
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A
djuvant endocrine therapy with tamoxifen has been recommended for premenopausal women with hormone-receptor–positive breast cancer (positive for es-trogen receptor, progesterone receptor, or both) during the past 15 years.1,2 The value of therapeu-tic suppression of ovarian estrogen production in premenopausal women who receive tamoxifen is uncertain.3 The American Society of Clinical On-cology endorsed guidelines recommending that ovarian ablation or suppression (hereafter, ovar-ian suppression) not be added routinely to adju-vant therapy in premenopausal women.4 Chemo-therapy-induced ovarian suppression (amenorrhea) is correlated with a reduced risk of relapse 5-7 but is less likely to be achieved in very young women. International consensus guidelines for breast-cancer management in young women suggested that the addition of a gonadotropin-releasing hormone (GnRH) agonist to tamoxifen be dis-cussed on an individualized basis.8In 2003, the International B reast Cancer Study Group (IBCSG) initiated two randomized, phase 3 trials, the Suppression of Ovarian Func-tion Trial (SOFT) and the Tamoxifen and Exemes-tane Trial (TEXT), involving premenopausal women with hormone-receptor–positive early breast cancer. SOFT was designed to determine the value of adding ovarian suppression to tamoxifen and to determine the role of adjuvant therapy with the aromatase inhibitor exemestane plus ovarian suppression in premenopausal wom-en. Here we report the results of the planned primary analysis in SOFT
9 comparing adjuvant tamoxifen plus ovarian suppression with tamoxi-fen alone after a median follow-up of 67 months.METHODS
PATIENTS The trial was designed to evaluate adjuvant endo-crine therapy in women who remained premeno-pausal after the completion of adjuvant or neo-adjuvant chemotherapy and in premenopausal women for whom adjuvant tamoxifen alone was considered suitable treatment. Eligibility criteria included documented premenopausal status, oper-able breast cancer, and tumor that expressed es-trogen or progesterone receptors in at least 10% of the cells (see the Supplementary Appendix, avail-able with the full text of this article at https://www.doczj.com/doc/0414074985.html,).Patients had to have undergone either a total mastectomy with subsequent optional radiother-apy or breast-conserving surgery with subsequent radiotherapy. Either axillary dissection or a senti-nel-node biopsy was required. Patients who had not received chemotherapy underwent random-ization within 12 weeks after definitive surgery. Patients who received chemotherapy before ran-domization and remained premenopausal were enrolled within 8 months after completing che-motherapy, once a premenopausal estradiol level was confirmed by a local laboratory. Patients were allowed to receive adjuvant oral endocrine therapy before randomization.STUDY DESIGN
Women were randomly assigned to receive oral tamoxifen at a dose of 20 mg daily, tamoxifen plus ovarian suppression, or oral exemestane (Aromasin, Pfizer) at a dose of 25 mg daily plus ovarian suppression. Treatment was for 5 years from the date of randomization, according to the study protocol, available at https://www.doczj.com/doc/0414074985.html,. Ovarian suppression was achieved by choice of triptorelin (Decapeptyl Depot [triptorelin acetate], Ipsen; or Trelstar Depot [triptorelin pamoate], Debio) at a dose of 3.75 mg administered by means of intra-muscular injection every 28 days, bilateral oopho-rectomy, or bilateral ovarian irradiation. Patients receiving triptorelin could subsequently opt to undergo oophorectomy or irradiation. Random-ization was performed by means of the IBCSG Internet-based system and was stratified accord-ing to prior chemotherapy (yes vs. no), lymph-node status (positive vs. negative), and intended
initial method of ovarian suppression, if as-signed. The assessments of the patients and the recording of adverse events followed a regular
schedule (see the Supplementary Appendix).The primary end point was disease-free sur-vival, defined as the time from randomization to
the first appearance of one of the following: re-currence of invasive breast cancer (local, regional, or distant), invasive contralateral breast cancer, second (nonbreast) invasive cancer, or death without recurrence or second cancer. Secondary end points included the interval without breast cancer, defined as the time from randomization to the recurrence of invasive breast cancer (local, regional, or distant) or invasive contralateral breast cancer; the interval from randomization to the recurrence of breast cancer at a distant site; and overall survival, defined as the time from randomization to death from any cause.The ethics committee at each participating
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center approved the study protocol, and all the patients provided written informed consent. The IBCSG was responsible for the trial design, data collection, and analysis. Pfizer and Ipsen, the re-spective manufacturers of exemestane and trip-torelin, donated the study drugs; neither manu-facturer imposed restrictions with respect to the trial data. The manuscript was written solely by the authors, who vouch for the data and analyses reported and for the fidelity of the study to the protocol. The steering committee (which included employees of Pfizer and Ipsen) reviewed the manuscript and made the decision to submit it for publication.STATISTICAL ANALYSIS The original statistical analysis plan for SOFT was to assess disease-free survival between the treatment groups with three pairwise compari-sons.9 The design assumed the enrollment of predominantly very young women who remained premenopausal after chemotherapy and would have an expected disease-free survival rate at 5 years of 67% when treated with tamoxifen, on the basis of outcomes for patients younger than 35 years of age in previous trials.9 The enrolled patients were older and had lower-risk characteristics than an-ticipated, and the rate of disease-free survival was higher than expected. A protocol amend-ment to the analysis plan was adopted in 2011, designating the test of the superiority of tamoxi-fen plus ovarian suppression over tamoxifen alone as the primary analysis for SOFT.9 We cal-culated that with an estimated 186 events of dis-ease recurrence, second invasive cancer, or death in the two treatment groups after a median fol-low-up of 5 years, the study would have at least 80%, 69%, and 52% power to detect reductions
in risk of 33.5%, 30%, and 25%, respectively,
with tamoxifen plus ovarian suppression versus tamoxifen alone, at a two-sided alpha level of 0.05. The comparison of exemestane plus ovarian suppression with tamoxifen alone became a sec-ondary objective, and the comparison of exemes-tane plus ovarian suppression with tamoxifen plus ovarian suppression was analyzed by means of a combined analysis with the TEXT data.10Analyses were performed according to the
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intention-to-treat principle. Kaplan–Meier esti-mates of time-to-event end points were calcu-lated. Hypothesis tests compared the two groups with the use of log-rank tests, stratified accord-ing to prior use of chemotherapy (yes vs. no) and lymph-node status (positive vs. negative). Strati-fied Cox proportional-hazards regression was used to estimate hazard ratios and 95% confi-dence intervals. In prespecified secondary analy-ses, heterogeneity of the treatment effect accord-ing to subgroup was investigated by tests of treatment-by-covariate interaction, and an ad-justed hazard ratio for the treatment effect was estimated.
R ESULTS
STUDY POPULATION
From December 2003 through January 2011, we randomly assigned 1021 premenopausal women to tamoxifen, 1024 to tamoxifen plus ovarian suppression, and 1021 to exemestane plus ovari-an suppression. After exclusions, 2033 women were included in the intention-to-treat popula-tion for the primary analysis comparing tamoxi-fen plus ovarian suppression with tamoxifen alone (Fig. 1, and Fig. S1 in the Supplementary Appendix). The median age of the patients was
43 years (Table 1). A total of 46.7% of the pa-
* A more complete summary is provided in Table S1 in the Supplementary Appendix. Characteristics were well balanced according to treatment assignment (Table S2 in the Supplementary Appendix). The statistical analysis plan did not specify hypothesis testing regarding comparisons between these groups. HER2 denotes human epidermal growth factor receptor 2.? Data were missing for 7 patients who did not receive chemotherapy and for 45 who had received chemotherapy previously.? Data were missing for 12 patients who did not receive chemotherapy and for 36 who had received chemotherapy previously.§ Oral endocrine therapy before randomization was allowed while premenopausal status was established or reestablished.
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tients had not received chemotherapy previously, and 53.3% received chemotherapy before ran-domization and remained premenopausal. Node-positive disease was present in 34.9% of the pa-tients.
EFFICACY
At a median follow-up of 67 months, 299 pa-tients (14.7%) had recurrent disease or a second invasive cancer or had died. The rate of disease-free survival at 5 years was 86.6% (95% confi-dence interval [CI], 84.2 to 88.7) among patients assigned to receive tamoxifen plus ovarian sup-pression, as compared with 84.7% (95% CI, 82.2 to 86.9) among those assigned to tamoxifen alone (hazard ratio for recurrence, second inva-sive cancer, or death, 0.83; 95% CI, 0.66 to 1.04; P = 0.10) (Fig. 2A). A total of 58.2% of the first events involved distant sites, and 12.0% were sec-ond (nonbreast) malignant conditions (Table S3 in the Supplementary Appendix). Planned sub-group analyses did not reveal heterogeneity of treatment effect across most subgroups (Fig. S2 in the Supplementary Appendix). However, the subgroup of patients with human epidermal growth factor receptor 2–positive tumors ap-peared to have a greater benefit with tamoxifen plus ovarian suppression than with tamoxifen alone. In the multivariable Cox proportional-haz-ards model, with adjustment for covariates, tamoxifen plus ovarian suppression significantly reduced the hazard of recurrence, a second inva-sive cancer, or death, as compared with tamoxi-fen alone (hazard ratio, 0.78; 95% CI, 0.62 to 0.98; P = 0.03) (Table S4 in the Supplementary Ap-pendix).At 5 years, 88.4% (95% CI, 86.1 to 90.3) of the patients assigned to receive tamoxifen plus ovar-ian suppression remained free from breast can-cer, as compared with 86.4% (95% CI, 84.0 to 88.5) of those assigned to receive tamoxifen alone (hazard ratio for recurrence, 0.81; 95% CI, 0.63 to 1.03; P = 0.09) (Fig. 3A). After adjustment for covariates in the multivariable Cox propor-tional-hazards model, tamoxifen plus ovarian suppression reduced the hazard of breast-cancer recurrence, as compared with tamoxifen alone (hazard ratio, 0.75; 95% CI, 0.59 to 0.96; P = 0.02). Among patients assigned to receive exemestane plus ovarian suppression, 90.9% (95% CI, 88.9 to 92.6) remained free from breast cancer at 5 years.Recurrence of breast cancer at a distant site was reported in 185 patients (9.1%), with no significant difference between those assigned to tamoxifen plus ovarian suppression and those assigned to tamoxifen alone (hazard ratio for recurrence, 0.88; 95% CI, 0.66 to 1.18; P = 0.40) (Fig. 3B ). Death was reported in 106 patients (5.2%); 4 patients died without a breast-cancer recurrence or a second invasive cancer. Overall survival at 5 years was 96.7% (95% CI, 95.2 to 97.7) among patients assigned to tamoxifen plus ovarian suppression and 95.1% (95% CI, 93.4 to 96.3) among those assigned to tamoxifen alone (hazard ratio for death, 0.74; 95% CI, 0.51 to 1.09; P = 0.13) (Fig. 2B).Among patients who did not receive chemo-therapy, more than 95% remained free from breast cancer at 5 years in each group (Fig. 3C), with few distant recurrences (Fig. 3D), and 32.9% of first events (a second invasive cancer or death) were not related to breast cancer (Table S3 in the Supplementary Appendix). Most recur-rences of breast cancer were in patients who
remained premenopausal after receiving chemo-
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therapy (Fig. 3E). In this cohort, the rate of freedom from breast cancer at 5 years was 82.5% (95% CI, 78.8 to 85.6) among those assigned to receive tamoxifen plus ovarian suppression and 78.0% (95% CI, 74.0 to 81.5) among those as-signed to receive tamoxifen alone (hazard ratio for recurrence, 0.78; 95% CI, 0.60 to 1.02). In the chemotherapy cohort, among patients assigned
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to exemestane plus ovarian suppression, 85.7%
(95% CI, 82.3 to 88.5) remained free from breast cancer at 5 years (Fig. 3E).Most recurrences of breast cancer at a distant site occurred in the patients who had received chemotherapy previously. The rates of freedom from distant recurrence at 5 years in this cohort were as follows: 83.6% among patients assigned to tamoxifen alone, 84.8% among those assigned to tamoxifen plus ovarian suppression, and 87.8% among those assigned to exemestane plus ovar-ian suppression (Fig. 3F).
More than 90% of the deaths occurred in pa-tients who had received chemotherapy previously. Overall survival at 5 years in the chemotherapy cohort was 94.5% (95% CI, 92.0 to 96.2) among
patients assigned to tamoxifen plus ovarian sup-pression, as compared with 90.9% (95% CI, 87.9 to 93.2) among those assigned to tamoxifen alone (hazard ratio for death, 0.64; 95% CI, 0.42 to 0.96) (Fig. 2B, and Fig. S5 in the Supplemen-tary Appendix).A total of 350 women younger than 35 years of age participated in the trial, 233 of whom were included in the primary analysis. Among these women, the rate of freedom from breast cancer at 5 years was 67.7% (95% CI, 57.3 to 76.0) for patients assigned to tamoxifen alone, 78.9% (95% CI, 69.8 to 85.5) for those assigned to tamoxifen plus ovarian suppression, and 83.4% (95% CI, 74.9 to 89.3) for those assigned to exemestane plus ovarian suppression. In this very young subgroup, 94.0% of the patients had
received chemotherapy previously.
TREATMENT AND ADVERSE EVENTS At a median follow-up of 67 months, 25.8% of the patients were continuing to receive some or all of the protocol-assigned treatment. Tamoxi-fen was discontinued early, with or without the substitution of alternative endocrine therapy, in 16.7% of the tamoxifen–ovarian suppression group and 21.7% of the tamoxifen group (Table S5 in the Supplementary Appendix). Rates of nonadherence with ovarian suppression were 5.0%, 9.2%, 14.9%, 18.3%, and 21.9% at 0.5, 1, 2, 3, and 4 years after randomization, respectively. Among patients assigned to ovarian suppression, it was achieved entirely through administration of the GnRH agonist triptorelin in 80.7% of the patients.Targeted adverse events of grade 3 or higher were reported in 31.3% of the patients assigned to receive tamoxifen plus ovarian suppression, as compared with 23.7% of those assigned to receive tamoxifen alone (Table 2, and Table S6 in the Supplementary Appendix). Hot flushes, sweat-ing, decreased libido, vaginal dryness, insomnia, depression, musculoskeletal symptoms, hyperten-sion, and glucose intolerance (diabetes) were re-ported more frequently in the tamoxifen–ovarian suppression group than in the tamoxifen group. Osteoporosis as defined by a T score of less than ?2.5 was reported in 5.8% of the patients as-signed to tamoxifen plus ovarian suppression and in 3.5% of those assigned to tamoxifen alone.DISCUSSION The results of SOFT show that, considering the entire population of patients who underwent
randomization, the addition of ovarian suppres-sion to adjuvant tamoxifen did not significantly improve disease-free survival. However, SOFT in-vestigated ovarian suppression in two distinct patient cohorts. The first cohort included 949 premenopausal women for whom adjuvant tamox-ifen without chemotherapy was considered to be suitable treatment. These patients were predomi-nantly older than 40 years of age, had small, node-negative tumors of low to intermediate grade, and had excellent outcomes with tamoxi-fen alone after a median follow-up of 67 months. The findings in this cohort do not currently in-form us about the clinical relevance of ovarian suppression because one third of the first events were not related to breast cancer, freedom from
recurrence exceeded 95% at 5 years, and addi-The New England Journal of Medicine
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tional recurrences are anticipated with further follow-up.
By contrast, the second cohort included 1084 women who remained premenopausal after com-pleting chemotherapy, as shown by estradiol measurement regardless of menses. The clinico-pathological features that warranted prior che-motherapy use 12 and the younger age of the women who remained premenopausal after che-motherapy (median age, 40 years) contributed to the higher risk of recurrence in this cohort than in the cohort that had not received chemother-apy. With a median of 67 months of follow-up, the number of breast-cancer recurrences ob-served was large enough to indicate that includ-ing ovarian suppression as a component of adju-vant therapy can meaningfully reduce recurrences in this cohort (Fig. 3E).
For women with ovarian estrogen production after chemotherapy, we had hypothesized that therapeutic ovarian suppression would provide a benefit similar to that observed with chemother-apy-induced amenorrhea.5-7 Resilience of ovarian function to chemotherapy correlates with young-er age. Chemotherapy-induced ovarian suppres-sion is common in older premenopausal women and is associated with improved breast-cancer outcomes.5-7 The SOFT design for the chemo-therapy cohort targeted younger patients by man-dating that only women who remained premeno-pausal or reverted to premenopausal status could be enrolled. Previous trials evaluating ovarian suppression were confounded by the inclusion of women who became permanently postmenopausal from chemotherapy or who had an unknown or negative hormone-receptor sta-tus; these trials also lacked a 5-year tamoxifen control group.13-15
When SOFT was planned, it was hypothesized that tamoxifen plus ovarian suppression would reduce the relative risk of breast-cancer recur-rence, a second invasive cancer, or death by 25%, as compared with tamoxifen alone, and further-more, that exemestane plus ovarian suppression would reduce the relative risk by 25%, as com-pared with tamoxifen plus ovarian suppression. After adjustment for covariates in the multivari-able Cox model, tamoxifen plus ovarian suppres-sion resulted in a 22% reduction in the relative risk of breast-cancer recurrence, a second inva-sive cancer, or death (P = 0.03) and a 25% reduc-
tion in the relative risk of breast-cancer recur-
* D a t a a r e f o r t h e 2011 p a t i e n t s i n t h e s a f e t y p o p u l a t i o n w h o r e c e i v e d a p r o t o c o l -a s s i g n e d t r e a t m e n t (e x c e p t f o r 3 p a t i e n t s w h o w i t h d r e w c o n s e n t w i t h i n 1 m o n t h a f t e r r a n d o m i z a t i o n a n d h a d n o a d v e r s e -e v e n t d a t a s u b m i t t e d ). T a r g e t e d a d v e r s e e v e n t s (22 e v e n t s ; s e e T a b l e S 6 i n t h e S u p p l e m e n t a r y A p p e n d i x ) a n d o t h e r a d v e r s e e v e n t s o f g r a d e 3 o r h i g h e r w e r e c a t e g o -r i z e d a c c o r d i n g t o t h e C o m m o n T e r m i n o l o g y C r i t e r i a f o r A d v e r s e E v e n t s , v e r s i o n 3.0.11 A d a s h i n d i c a t e s t h a t g r a d e 3 o r 4 w a s n o t a p o s s i b l e g r a d e f o r t h e s p e c i f i e d a d v e r s e e v e n t . T h e r e w a s o n e t a r g e t e d a d v e r s e e v e n t o f g r a d e 5 (c a r d i a c i s c h e m i a o r i n f a r c t i o n i n a p a t i e n t r a n d o m l y a s s i g n e d t o t a m o x i f e n ).? G l u c o s e i n t o l e r a n c e (d i a b e t e s ) w a s a d d e d a s a t a r g e t e d a d v e r s e e v e n t i n 2011 a n d t h e r e f o r e m a y b e u n d e r r e p o r t e d .? T h e c a t e g o r y o f a n y t a r g e t e d a d v e r s e e v e n t i n c l u d e s t h e 22 t a r g e t e d a d v e r s e e v e n t s s u m m a r i z e d i n T a b l e S 6 i n t h e S u p p l e m e n t a r y A p p e n d i x .
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rence, as compared with tamoxifen alone. After a protocol amendment, the comparison of ex-emestane plus ovarian suppression with tamoxi-fen plus ovarian suppression, on the basis of a combined analysis with TEXT, showed a 28% reduction in the relative risk of breast-cancer recurrence, a second invasive cancer, or death and a 34% reduction in the relative risk of breast-cancer recurrence in the exemestane–ovarian suppression group (P<0.001).10Overall, tamoxifen plus ovarian suppression resulted in an absolute improvement of 2.0 per-centage points, as compared with tamoxifen alone, in the proportion of patients without re-current breast cancer at 5 years. In the higher-risk cohort of patients who remained premeno-pausal after chemotherapy, tamoxifen plus ovarian suppression resulted in an absolute improvement of 4.5 percentage points, as compared with tamoxifen alone, in the proportion of patients without recurrent breast cancer at 5 years; with exemestane plus ovarian suppression, the abso-lute improvement was 7.7 percentage points, as compared with tamoxifen alone. These observed relative and absolute benefits at 5 years from ovarian suppression plus tamoxifen or ovarian suppression plus exemestane, as compared with tamoxifen alone, compare favorably with the practice-changing results of randomized trials of adjuvant aromatase inhibitors versus tamoxi-fen in postmenopausal women.16Patients who receive a diagnosis of hormone-receptor–positive breast cancer when they are younger than 35 years of age are a subgroup considered to be at higher risk for adverse out-comes than are older premenopausal women, on the basis of retrospective analyses of data from IBCSG and U.S. Intergroup trials.17,18 The results observed in this subgroup in SOFT add to the evidence that ovarian suppression plays an impor-tant role in younger premenopausal patients.13-15 Among the women younger than 35 years of age, breast cancer recurred within 5 years in ap-proximately one third of the patients assigned to receive tamoxifen alone but in one sixth of those assigned to receive exemestane plus ovarian sup-pression.Any benefit from ovarian suppression must
be weighed against the adverse effects. Adding ovarian suppression to tamoxifen resulted in increased adverse events — most notably, meno-pausal symptoms, depression, and adverse events with possible long-term health implica-tions such as hypertension, diabetes, and osteo-porosis. When exemestane is combined with ovarian suppression, adverse sexual, musculo-skeletal, and bone-density effects are more frequent than with tamoxifen plus ovarian sup-pression.10Longer follow-up is required, because SOFT
is currently underpowered, and the overall sur-vival analysis is premature after 5% of patients have died. The combined analysis from TEXT and SOFT showed that adjuvant endocrine therapy with ovarian suppression plus exemes-tane is significantly more effective than ovari-an suppression plus tamoxifen.10 The current analysis indicates that in a cohort selected for chemotherapy and persistent premenopausal status, ovarian suppression plus tamoxifen im-proves outcomes, as compared with tamoxifen alone, with the most striking differences ob-served among younger patients.We conclude that adding ovarian suppression to tamoxifen did not provide a significant benefit in the overall population of premenopausal wom-en in this trial. However, in the cohort of women who had a sufficient risk of recurrence to warrant adjuvant chemotherapy and who had premeno-pausal estradiol levels despite chemotherapy, ovar-ian suppression in addition to tamoxifen reduced the risk of breast-cancer recurrence, as compared with tamoxifen alone. Ovarian suppression com-bined with an aromatase inhibitor further re-duced the risk of recurrence, as compared with tamoxifen-based therapy, in this higher-risk pre-menopausal cohort.
Supported by Pfizer, Ipsen, the International Breast Cancer Study Group, and the National Cancer Institute.
Disclosure forms provided by the authors are available with the full text of this article at https://www.doczj.com/doc/0414074985.html,.
APPENDIX
The authors’ affiliations are as follows: the Peter MacCallum Cancer Centre, St Vincent’s Hospital, University of Melbourne, Melbourne, VIC (P.A.F.), the Australia and New Zealand Breast Cancer Trials Group, University of Newcastle, Newcastle, NSW (P.A.F., A.S.C.), and the University of Sydney, Sydney (A.S.C.) — all in Australia; the International Breast Cancer Study Group (IBCSG) Statistical Center, Dana–Farber Cancer Institute (M.M.R., A.G.-H., R.D.G.), Harvard Medical School (M.M.R., R.D.G.), Susan F. Smith Center for Wom-en’s Cancers, Dana–Farber Cancer Institute, Harvard Medical School and Alliance for Clinical Trials in Oncology (H.J.B., E.P.W.), IBCSG Statistical Center, Frontier Science and Technology Research Foundation (K.N.P.), and Harvard School of Public Health, Frontier
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Adjuvant Ovarian Suppression in Breast Cancer
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Science and Technology Research Foundation (R.D.G.) — all in Boston; University of Chicago Medical Center and Alliance for Clinical Trials in Oncology, Chicago (G.F.F.); National Institute of Oncology and International Breast Cancer Study Group, Budapest, Hungary (I.L.); University Hospital 12 de Octubre, Madrid (E.C.), Vall d’Hebron Institute of Oncology and Vall d’Hebron University Hospital (M.B.), and SOLTI Group (E.C., M.B., M.A.C.), Barcelona, and Instituto Valenciano de Oncologia, Valencia (M.A.C.) — all in Spain; Institut Bergonié Comprehensive Cancer Center, Université de Bordeaux, INSERM Unité 916, Bordeaux (H.R.B.), and Centre Eugène Marquis, Université de Rennes, Rennes (P.K.) — both in France; European Organization for Research and Treatment of Cancer, Brus-sels (H.R.B., P.K.); Salvatore Maugeri Foundation and IBCSG, Pavia (G.A.D.P.), and the European Institute of Oncology and Interna-tional Breast Cancer Study Group (M.C., A.G.) and IBCSG Central Pathology Center, European Institute of Oncology, University of Milan, Milan (G.V.) — all in Italy; the Angeles Clinic and Research Institute and SWOG, Santa Monica, CA (S.M.); University of Pitts-burgh Cancer Institute, University of Pittsburgh Medical Center CancerCenter, and the ECOG–ACRIN Cancer Research Group, Pitts-burgh (N.E.D.); Massey Cancer Center, Virginia Commonwealth University School of Medicine and NRG Oncology, Richmond (C.E.G.); Tom Baker Cancer Centre and National Cancer Institute of Canada Clinical Trials Group, Calgary, AB, Canada (B.A.W.); Weston Park Hospital, Sheffield, and National Cancer Research Institute Breast Cancer Clinical Studies Group and Institute of Cancer Research Clinical Trials and Statistics Unit, London — all in the United Kingdom (R.C.); German Breast Group and the Department of Obstetrics and Gynecology, University Medical Center Regensburg, Regensburg, Germany (S.B.); Mayo Clinic and Alliance for Clinical Trials in Oncology, Rochester, MN (J.N.I.); and University Hospital Inselspital (M.R.-P.) and IBCSG Coordinating Center (M.R.-P., R.M., B.R.), Bern, Switzerland.
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新模式英语第一册unit1lesson1-2 广东省xxx学院广东省xxx学校理论课教案编号：NGQD-0707-09版本号：A/1页码：1编制/时间:审核/时间：批准/时间：课程名称NewModeofEnglish课题Unit1Talkingwithothers:Whereareyoufrom?Whatdoeshelooklike?授课班级1263FoodEngineeringandTesting授课日期2013.4.15/18授课时数4教学类型NewLesson教学方法Grammar-TranslationCommunicativeSituational教材及参考资料Textbook教学目标StudentscangivepersonalinationanddescribepeopleStudentsmastergra mmarpointhis/hersimplepresent:have;adjectiveorder教学重点及化解方法重点：Askandgivepersonalination化解方法：Dorcisestoreinforcewhatstudentshavelearn教学难点及化解方法难点：Grammarpoint:theusageofsimplepresent化解方法：DrillstudentsbyaskingquestionsaboutthepicturebelowthechartFonpag e3andaboutthemselves.Helpstudentstousecompletesentences.Writeth eirresponsesontheboardincompletesentences.教学准备laptop,teachingplanning教学对象分析Thereare32studentsinthisclass.Mostofthestudentscankeepsilentandlis tentotheteachercarefully,afewstudentshaveabadknowledgebasement, Duringtheclass,somestudentsaretooshytoopentheirmouthtospeakout.广东省xxx学院广东省xxxx学校理论课教案编制/时间：页码：
新课标下高效的英语课堂教学模式 发表时间：2014-08-04T16:58:14.530Z 来源：《科教新时代》2014年7月供稿作者：陈志堂[导读] 进一步引导教师教学观念的转变，全面促使教师自觉地、富有创造性地投入到教学变革之中，并以此为统领，有效地将“三维”目标落实到课堂教学之中。贵州省福泉市地松初级中学陈志堂 【摘要】高效能课堂教学旨在提高课堂教学的效率和效力。所谓效率是指在单位课时内完成教学任务的量；效力是对完成教学任务在质的方面的要求。我们以《英语课程标准》中提出的 “要实现学生在语言技能、语言知识、情感态度、学习策略和文化意识等方面的综合发展”为总目标，积极探索转变教学观念，改变教学方法，优化英语教学过程，着眼于学生英语综合能力的提高，培养学生的文化意识和全球意识，使他们形成良好的学习态度和学习习惯，为他们的终身发展打下坚实的基础。【关键词】高效；课堂教学；英语【中图分类号】G533.40 【文章标识码】D 【文章编号】1326-3587（2014）07-0030-01 一、研究目标新的课程改革的核心目标是实现课程功能的转变，就是要改变课程过于注重知识传授的倾向，强调形成积极主动的学习态度，使获得知识与技能的过程成为学会学习和形成正确价值观的过程。实现这样三位一体的课程功能，探究性学习是一个比较理想的载体，它有利于学生主动探究、乐于合作，形成积极的情感体验，有利于他们主动发现问题、分析和解决问题，形成良好的学习习惯。这种学习方式的转变将帮助学生学会学习，为终身学习做好准备。 二、追求学生学习方式的转变 《基础教育课程改革纲要》中指出：“改变课程实施过于强调接受学习，死记硬背，机械训练的现状，倡导学生主动参与，乐于探究，勤于动手，培养学生搜集和处理信息的能力，获取新知识的能力以及交流与合作的能力。”探究性学习就是要开发学生的潜在能力，让学生在开放、愉悦的学习环境中，运用多渠道的学习资源，增强实践动手能力和观察发现能力，培养探究和创新的综合运用能力，真正让学生从“灌输式”的枷锁下解放出来，成为一名“知识与能力的融和型”人才。当然英语教育提倡探究性学习方式，但也不能排除接受性学习。英语教育中有意义的接受性学习要与探究性学习整合使用，协调发展。 三、追求学生科学性和人文性的整合发展 社会的发展靠人的发展推动，人的发展除了要掌握认识自然和社会、改造自然和社会的科学知识外，还必须发展人的思想道德、情感意志、科学态度、价值取向、合作分享等人文素质。英语学科探究性学习要求英语课堂教学紧密联系现实世界和社会以及学生的生活实际，让学生亲自参与运用英语探究、解决问题的过程。这样不仅能促进学生的英语知识和运用知识的系统化和结构化，同时也能加深思想观念、情感意志、科学态度、价值取向、互助合作和团队精神等方面的人文性的感悟和体验，使科学性和人文性协调发展、整合发展。 四、追求学生实践能力和创新精神的发展 探究性学习为学生提供参与实践活动的客观情境。在真实的情境中学生运用英语发现问题、提出问题，调查研究，查阅文献获取信息，并对信息进行分析判断处理，进而解决问题。学生亲自实践活动的过程不仅获取了实践能力，也感染了积极的情感意志，丰富了创新精神的体验。 五、追求学生素质和个性的全面发展 传统英语教学以书本、教师和课堂为中心，忽视学生德智体美劳全面素质和个性的健全发展。不同于这种消极被动的接受知识的学习方式，探究性学习根据学生认知心理结构、能力结构、情感意志、策略方法和经历体验的个性差异，重视因材施教，发展每一个学生的个性。采用探究性学习方式，学生可以在真实的情境中积极主动地参与师生、生生之间的合作探究交流活动，从而不断获取知识、技能和能力，发展学生的世界观、人生观和价值观。 六、存在的问题及解决办法 （一）存在的问题。 1．课程改革的许多新理念，要落实到课堂教学活动中，实践时，许多教师还相对稚拙。教学的进程是非线性的，教师要有应对变化、滋生教学的基本功。这对教师的专业水平提出了更高的要求。要真正把认识和行动统一到课程改革的思想上来，教师需要有专业指导，必须坚持理论与实践的统一，着眼于研究的科学性。 2．学生经过几年的学习，尤其是进入初三年级的时候，出现了两极分化现象：一部分学生学习能力强，学习成绩好，学习兴趣也更浓；而另一部分学生则学习能力低，学习成绩越来越差，也就越来越失去了学习英语的兴趣。其表现在听说尚可，但读写则很难。 3．学生的读写能力还有待加强。从整体上看，学生的读写能力普遍较差，还不能很好地独立完成学习任务，需要在教师的指导下才能完成，因此，他们这方面的能力还有待提高。 (二)解决办法。 1．进一步引导教师教学观念的转变，全面促使教师自觉地、富有创造性地投入到教学变革之中，并以此为统领，有效地将“三维”目标落实到课堂教学之中。 2.教师应多向学生推荐一些图文并茂的英文读物，鼓励学生进行课外阅读，精挑细选一些幽默故事、笑话等英文材料，激发学生的阅读兴趣，提高学生的阅读能力。回首近年课题研究历程，我们更加意识到，科研是完善教育、完善人的重要载体和途径，是学校得以持续发展的强大驱动力，是显示现代教育魅力之所在。我们将不负众望，求实务真，积极创新，努力谱写出有关初中英语课堂教学有效模式建构理念的新篇章。
工程款支付审批流程 1.目的 为了加强工程款支付管理，规范工作流程，确保工程资金安全、有效的使用，特制定本审批流程。 2.适用范围 本管理办法适用于所有项目工程款支付的管理。 3.职责 技术管理组主要负责对施工单位所申报工程款是否达到合同约定的支付条件进行 审核确认，对工程形象进度、工程质量、工程资料、已完工程量及到场材料设备数量的确认；办公室主要负责复核工程形象进度、已完工程量及到场材料设备数量以及应支付工程款的确定；院财务科根据审批确认的应付款额进行工程款的支付与扣回。 工程总监根据工程项目部及成本控制的审核意见提出对本次进度款支付的审核意见； 工程项目技术组施工单位申报工程款是否达到合同约定的支付条件进行审核确认，对工程形象进度、工程质量、工程资料、已完工程量及到场材料设备数量审核确认负全面责任； 跟踪设计单位根据工程项目部及成本控制造价人员的审核意见提出对本次进度款支付的审核意见； 技术管理组材料负责人对自身负责的材料及设备供应工程款的审核确认负全面责任; 财务人员对自身负责的工程款的支付及扣款负全面责任。 4．工程进度款的支付 具备申请付款的条件： 按合同约定需支付预付款；工程达到合同约定形象进度；工程质量经验收达到合 同约定要求；相关工程资料齐全等。 工程进度款的确认及支付审批流程： 4.2.1施工单位在工程达到合同付款条件后按合同约定期限向监理公司提交《工程进度款支付申请书》（含工程形象进度说明、工程质量验收合格证明文件、已完工程内容及相应数量、已完产值的计价书等）；若为分包单位，其《工程进度款支付申请书》在提交监理公司前须总包单位签署审核意见。 对施工单位提交的《工程进度款支付申请书》中内容在1个工作日内进行核实确认，并在《工程款支付审批表》中签署审核意见（主要包括形象进度的确认、是否达到合同约定付款条件、已完工程质量以及已完工程量的确认、应扣款项、相关工程资料是否齐全等）后将所有资料交跟踪审计单位； 跟踪审计单位对监理部报送的《工程款支付审批表》及《工程进度款支付申请书》在3个工作日内进行审核确认并签署审核意见（主要包括形象进度的确认、是否达到合
中美小学教育比较 一、课程设置 中国小学思想品德课程占全部课程3.9%，美国小学不开设思想品德课； 中国语文占全部课程25%，美国占38%； 中国算术20%，美国占23%； 中国科学课占4.7%，美国占3%； 中国地理课和历史课都占1.6%，美国小学地理课和历史课教学都溶入社会教育之中； 中国小学不开设社会学习课，而美国小学社会学习课程占全部课程13%； 中国小学体育课占全部课程7.8%，美国占10%； 中国小学音乐和美术课程占14%，美国占13%； 中国小学劳动课程占1.6%，而美国小学则不开设劳动课程。 从课程开设来看，中美小学对本国语言课程重视程度区别较大，其次是思想品德教育，美国规定在课堂上不得宣讲宗教信仰，宗教信仰是个人自由，应该由家长向子女传授。 二、教师要求 中国小学教师大多是高中或师范毕业生，而美国小学教师要求至少是大学毕业； 中国小学教师平均月工资是$250，美国小学教师月工资则达人均$4000； 中国政府每年为每位小学生投入$81，美国则多达$4563； 中国小学每班通常都达到70人左右，而美国小学每班人数不得超过33人； 中国小学文化课学习水平通常都要比美国小学生高出两级，即中国小学二年级学生水平与美国小学四年级学生水平相当。 中国小学教师一般情况下只教授一门课程，而美国小学实行包班制，即某一个班所有课程全部由一位老师承担。 从这里看出，两个国家对小学教师入职要求区别很大，对教育投入区别也非常大，美国实行是真正免费义务教育，而中国义务教育由于政府投入不足，很多收费任由学校收取，导致义务教育阶段乱收费问题屡禁不止。
三、课堂教学 中美两国小学教育最大区别要数课堂教学了。 首先是班额差别大，中国小学通常都是第班60人左右，少数地区班额高达80人，美国小学班额则不会超过30人； 中国课堂中学生规矩守纪，教师传授知识，学生认真听讲，美国课堂中学生自由活跃，学生或席地而坐，或随意走动，教师启发学生思考和讨论问题，学生思维活跃，课堂气氛热烈。 虽然近几年中国课堂教学改革使课堂教学模式稍有改变，但应试教育根基并没有动摇；中国课堂教学内容深，要求高，重点放在培养学生解题能力方面，而美国课堂教学内容相对来说要浅得多，重在培养学生思维能力。
中国与美国的基础教育的对比 摘要：本文将对比中国和美国在基础教育方面的差别，分析中美基础教育的不同之处，简要分析产生差距的原因。 关键词：基础教育；中美差距；原因 1中美基础教育的历史背景 1.1中国：在中国古代文献中，教育一词最早见于《孟子·尽心上》中“得天下英才而教育之”，教育就是教诲培养的意思。是人类文化传播的首要手段，为中国教育的成功奠定了基础。在私学兴起之前，那时的教育由官府控制，在私学兴起之后，受教育的对象不止仅限于贵族阶级，扩大平民百姓，因为私学的产生，教师可以自由选择地点教学，学生亦可以选择教师来学习，为当时的教育普及发展做出了很大的贡献。由于出现了许多不同的私学，不同派系不同主的私学出现了相互抗衡，相互补充的百家争鸣的盛况，极大丰富了当时的文化发展。经过了许多朝代教育的发展，教育与政治的关系逐渐加强，学而优则仕的观念深入人心，特别是在汉武帝为加强中央集权而推行的儒学教育，从中央到地方都以儒学为尊的思想影响着后来的基础教育发展。古代“小学”教育的主要容是识字，写字，习经史，学六艺等，检查学生的学业情况也靠考试，在宋代有“日考”，“月考”，“季考”等多种考试方法。受当时科举考试制度的影响，童生学习的容也相对固定，固定的背诵考试相关的篇目，全然不顾理解与否，而考查方式也很简单，以考生能否背诵来判断是否学好，借以选拔进入下一阶段的学习。 1.2美国：美国是最早实行义务教育的国家，早在十九世纪，美国就普及了小学教育，在之前17世纪初，首批欧洲移民在北美大陆定居下来以后，教育活动随之开始，由于新英格兰地区的移民大多是英国的清教徒，他们崇尚书本并信奉教育，所以新英格兰地区的教育活动最为活跃，对日后的美国教育特色的形成和发展的影响也最为突出。自19世纪初到20世纪80年代末，美国为支持教育的发展已经经历了四次大的革命浪潮：第一次教育改革是在美国在其教育体制不完整且带有强烈的殖民性和色彩的情况下发起的，这次革命主要是对教育的容世俗化，初等教育的公立化和学校序列的体系化做出的改革，使得当时公立小学和中学普遍建立起来，初中高各级学校互相衔接的机制得以健全。第二次教育改革为了应对充满激烈竞争和公立主义的垄断资本主义社会的各种问题，美国发起了进步主义教育运动，提出了“全儿童”的概念，反对唯智主义，很大程度上成为美国教育思想的主流。第三次国防教育法改革和第四次“国家危险”改革促使美国教育的进步。 2中美基础教育理念 2.1中国基础教育侧重公平，统一：由于中国人口众多，地域广阔，不同地方的教育发展状况不一，为了让全体国民都享有一定的受教育的权利，政府在基础教育阶段的政策主要是为了保证基础教育水平都稳步提升。像法国，前联以及中国在课程决策上具有集权化的传统, 强调中央对课程的开发、管理与控制，课程权力高度集中于中央,课程几乎完全由国家决定,地方和学校都没有课程决策的权力,只能执行国家的决定，保证全国教育的基本水平。这种教育的理念使政府把很大的精力放在保障弱势群体和贫困群众的教育水平，虽然教育的差距任
杨屯联校三段·六环节英语课堂教学模式三段·六环节即：1、课堂准备阶段（Step1. Warming-up╱Revision） 2、精讲多练阶段（Step2.Presentation ，Step 3.New lesson，Step4.Practise） 3、巩固发展阶段（Step5. Check and extension ，Step6．Summary） Step1. Warming-up╱Revision 有读有演，有张有弛，循序渐进，温故知新。 （1）温习单词环节： 上英语课时，学生按单词表的顺序用升、降调领读单词两遍、汉语一遍。每个学生熟读后，要求齐读。通过周而复始地训练，到期中监测时，每个学生能背出一至五模块的单词 期中监测后，再按以上方法领读六至十模块的单词。到期末监测时，每个学生都能背出一至十模块的单词。不同英语水平的学生见词会读，多数学生还能见词说句、即兴表演。 （2）朗读课文环节 每堂课，学生要朗读学过的一个模块（下一节课接着这个模块继续读）。如：五年级已学到第五模块时，本周的第一堂课读第一模块，第二堂课读第二模块，以此类推。读时，找一个学生领读标题，其他学生齐读正文。这样反复进行朗读，有利于学生把学过的知识稳扎稳打，同时也提高了学生的口语交际能力 Step2.Presentation 单词学习 （1）首先教师以图片或事物的形式教授新单词，学生通过跟师读，点读笔读，来初步接触新单词，并模仿标准的语音语调，师给予指导。 个人细读、背诵一段时间后，各小组进行组内检查。组内检查由组长组织，组长先读或背诵，再是副组长、组员依次轮流。采用这样形式，小组团结一致，合作愉快，发现问题会及时相互共同解决，还能帮助学习有困难的同学不掉队。 强化巩固单词时，我们要求学生：1）心里想着这个单词的汉意。2）眼睛看着单词的字母组合。3）口里读着单词的音。4）手指笔划着字母组合。 这样通过小组的合作练读，减少了学生自读时遇到的困难, 避免了学生自读时的枯燥无味。小组合作愉快，学生积极性高，个个乐不疲惫，几乎没有掉队的，达到了事半功倍的效果。
工程进度款支付的审批流程 一、审批流程： 1、施工单位→监理公司→建设单位：○1现场主管工程师○2现场预算人 员○3建设单位项目部→公司预算部 二、所用的表格和资料： 1、施工单位： ○1施工单位应填写工程款支付申请表。(附件一) ○2附工程量清单。相对应已完工程量的预算书。 ○3所报的表格和资料一式四份。 2、监理公司： ○1审核已完工程量是否属实。 ○2根据审核的已完工程量填写《工程款支付证书》。（附件二） 3、建设单位： ○1首先由现场工程师（水电工程师签署水电扣款金额）在《项目部工程款支付审批表》上签署意见。 ○2公司成控部在现场的预算人员再次对已完成的工程量进行审核，并在《项目部工程款支付审批表》上签署意见。 ○3项目经理在《项目部工程款支付审批表》中填写拟办意见。 ○4填写完的《项目部工程款支付审批表》及附件转交公司成控部。 三、所用表格的名称： 1、工程款支付申请表。（附件一，施工方用表）。 2、工程款支付证书。（附件二，监理用表）。 3、项目部工程款支付审批表。（附件三，建设方用表）。
四、用表附后：
项目部工程款支付审批表 所属公司：2011年月日 支付：年月日——年月日：月份工程款 项目名称附件合同名称1、 承包单位2、 水电费请成控部按月扣回水电费3、其他应扣款4、现场主管工程师 意见 水电工程师 意见 成控部意见 （现场预算员） 项目经理 意见 财务部 意见 副总经理 意见 总经理 意见 董事长 意见 备注1、工程款支付审批时，附件如下：①请款单位《工程款支付申请表》。②附工程量清单。相对应已完工程量的预算书。 2、附监理公司的工程款支付证书。
美国中小学课程设置 1.小学教育的培养目标 美国没有全国统一规定的小学教育目标，不过美国视导和课程研究协会提出的现代小学的六项任务，具有广泛的影响，大致内容为：①增进儿童的健康和发展儿童的体格；②增进儿童的心理的健康和发展儿童的人格；③发展儿童对社会和科学世界的认识；④发展儿童有效参与民主社会的技能；⑤发展儿童符合民生生活的价值观；⑥发展儿童的创造性活动。 2.小学课程的管理与设置 美国各州的公立中小学课程是由州宪法和州教育法规定，因此全国没有统一的课程。20世纪80年代以来由于高质量教育改革的实施，要求加强课的统一性的主张开始出现，但基于美国长期以来的地方分权化教育管理传统不可能完全建立全国统一课程，中小学课程的决策仍主要在各州及各个学校。现行美国小学通常都开设如下的基本核心科目： (1)语言艺术。(2)社会。(3)数学。(4)科学。(5)体育和保健。(6)音乐和艺术教育。 3.授课时数 美国各州小学每学年的授课天数相差很大，每天的授课时数也不一样。通过对某些学校的统计发现，学生从低年级到高年级，平均每天在校上课时间逐渐增加。小学的课程编排非常灵活。各节课的时间长短变化较大，有些课长达1 小时，而某些课仅20分钟。美国小学虽然实行5天教学日，但它在一天之中的课节数较多，每天上课的总时间较长。 现行美国小学课程受20世纪80年代以来高质量教育改革的影响，倡导以学术为中心，重视培养学生掌握各种基础知识、基本技能，发展学生的思维能力；从课程组织形式来看，小学阶段以综合课为主：语言艺术包含了阅读、写作、文学、口语等知识，社会包括了历史、地理、政治、法律等方面的知识，科学课将物理、化学、生物等方面的知识融为一体，音乐与艺术、体育和保健也具有较明显的综合课的特点。 (二)中学课程 1.中学教育的培养目标 关于美国中学教育的培养目标，最有影响并经常被引用的仍然是美国中等教育改组委员会提出的“七大原则”：①保持身心健康；②掌握学习基本技能；③成为家庭有效成员；④养成就业技能；⑤胜任公民责任；⑥善于运用闲暇时间；⑦具有道德品质。 2.中学课程的结构 美国主要有三类学校，即四年制中学、三三制中学和中间学校，其中三三制中学最为普遍，分为初中和高中，主要围绕教学、指导和服务三方面来进行，主要是教学工作。美国中等教育的教学科目非常庞杂，全国中学阶段学科多达247种，有必修和选修之分。课程一般分为两类：一类是学术性科目，如英语、社会学科、理科、数学、外语、人文学科；另一类为非学术性科目，如卫生、体育、家政、音乐、美术、工艺等。实行学分制，学生须修满16学分方准毕业。 美国中小学课程的发展趋势及启示 (一)美国中小学课程的发展趋势 为了保证美国在国际社会中的竞争地位，美国总统和五十个州首脑在1990年2月正式通过了《全美教育目标》的报告，提出了迈向21世纪全美教育的六大目标：“①为所有孩子做好入学前的学习准备；②降低中学生辍学率，高中毕业率至少要提高到90%；③学生在中学毕业时，应在英语、数学、科学、历史、地理各学科方面具备应有的知识和技能；④美国学生在科学、教学方面的成绩成为全球第一；⑤每个成人都将是有文化、精于读、写、算的人，并掌握在全球经济竞争及履行公民的权利和义务所必需的知识和技能；⑥所有学校都将成为无吸毒、无暴力的场所，为学生的学习提供有利的、纪律得以保障的学习环境。
篇一：赴美考察报告 赴美考察报告 王文郁 2011年1月31日 美国基础教育考察报告 济宁学院附小王文郁 2011年初，山东省教育厅组织了“山东省齐鲁名师培训团”赴美考察。全团共25人，徐曙光同志任团长，王景华、吴建华同志任副团长，负责全团赴美考察工作。培训团全体成员在济南经过行前培训后，于1月5日赴美国开展了为期21天的考察工作，途径了纽约、华盛顿等地，在康州对美国的基础教育进行了重点考察培训。培训团圆满地完成了考察培训任务后，于1月25日返回国内。 我参观考察的三所学校分别是eastlyme school、salem school、lyme school，并主要在salem school参观学习。这是一所集幼儿园、小学、初中为一体的乡镇小学。下面所描述的现象只是我在这三所学校的所见所闻，不能代表美国的整个教育现状，但从中可以感受美国教育的一面。 一、美国的基础教育情况 （一）、美国的教育体制 1、管理权利分散，不统一。地方、州政府、联邦政府三级机构各有权利范围。地方权利即学校董事会，是由地方热爱、关心教育的公民选出来的。学区总监选聘校长，校长选聘老师，所有聘任人员都由学校董事会通过。 2、管理权利集中在底层而非上层。教育经费来源地方和州政府。 3、每个孩子不管智商和体质有多大差别，都有受教育的权利。 4、美国强调发展个性。（中国强调集体。） （二）、美国的教育方法 1、美国强调有助于发展受教育者个性和创造性的教育方法。 2、教师在教室里做哪些事对学生成长有帮助，作为校长评价老师看以下三点： ①教育指导是否有有效措施。 ②看老师怎样布置教室。是否能调动所有积极性促进学生。③老师如何设计课程。 美国对到毕业达到什么水平有规定，但没有全国性的统一课程，有的地方或老师自己设定课程。老师更多考虑：让学生学什么？学生已知什么？怎样把学生已有知识和要学知识联系起来。 美国老师侧重： 1让学生认识到所学内容知识和事物间的相同点和不同点。2教学生总结和记录。 3鼓励学生参和的兴趣。 4研究怎样给学生留作业，怎样训练学生。 5利用非文字的东西进行教学。 6鼓励学生小组学习，一起解题或完成某个项目。 7提供学习目标，并将学习情况给学生反馈，据学习目标，学生能较好考评自己。 8提出假设并让学生证明假设。 9提出高质量的问题，给学生有效地引导。 （三）、美国学校特点 1、教室小班额，每个教学班的学生有20人左右，一般是6—25不等。我所参观的学校，每班人数大约13——18人，实行个性化教育。 2、走班制。学校班级的组成，不像我们有固定的行政班，而是以学科为特点的教学班，如语文教室、数学教室、美术教室、音乐教室、外语教室等。老师是定班制即一直在自己学科教室上课，学生是走班制即按课表走动到不同的学科教室上课。学生没有固定的教室，3-5分钟实现换教室。学生很匆忙，学校里就是抓紧时间去学习，也给学校管理带来方便。
美国教育与中国教育的区别 美国学生与中国学生教育的十大区别 1、考上大学 美国学生为了能从大学毕业，上了大学才开始好好学习，中国学生为了考上大学而拼命学习，上了大学就不再好好学习。（注：美国大学“宽进严出”；中国大学“严进宽出”） 2、向老师发问 在课堂上，美国学生为了装懂而向老师发问，还认为坐的横七竖八才能更好与老师交流。 中国学生则为了装懂而不向老师发问，还认为坐的端端正正是对老师的尊敬。 3、解题方法 如果老师给出同一道题目：“现在是12点整，时针和分针正好重合，请问要经过多长时间时针和分针才能再次重合？”老师语音刚落，美国学生的反应是不约而同的拨动腕上的手表，用这种其实很聪明的“笨方法”，看时针和分针什么时候才能再次重合。而在场的中国学生立即拿出纸和笔，埋头列出一大堆公式并开始计算。 4、受教育方式 美国学生的受教育方式是“放羊”，十分轻松，所以他们大多数喜欢异想天开，想象力无比丰富。中国学生的受教育方式是一种“填鸭”，辛苦的很，题海战术他们不怕，怕就怕那种脑筋急转弯的问题，因为有的时候，他们确实转不过弯来。 5、数学头脑 美国学生一般不大有数学头脑，不得不长期依赖电子计算器。 中国学生都是数学天才，口算心算水平一流。 如果中国学生告诉美国学生，我们能够不用计算机做四位数的乘除法，甚至能够徒手开平方根，那美国学生看中国学生的眼神，肯定像看见了撒谎的小木偶的长鼻子一样。 6、零用钱 美国学生的父母说：“我们不得不通知你，你这个月的零用钱已经超出预算了。去，把车库打扫一下，把游泳池刷一刷，或把家里打扫一遍，我们就可以在给你一些零用钱。” 中国学生的父母说：“零用钱用完了吗？没钱就自己到抽屉里去拿。” 7、旅游 美国学生对自己的父母说：“我已经攒够钱了，我要去旅游了。” 中国学生对自己的父母说：“我要去旅游了，请给我一笔钱。” 8、女朋友 美国学生把女朋友带回家自豪的对父母说：“这是我女朋友。” 中国学生面对着自己已经被撬开的日记，看着气急败坏的父母，心虚的说：“我没有早恋·····” 9、新赛车 美国学生喜欢夸耀自己：“瞧，这是我自己组装的新车。” 中国学生喜欢夸耀自己的长辈：“看，这是我爸爸给我买的新车。” 10、自己做主 美国学生的父母对他们说：“亲爱的，你已经长成一个男子汉了，自己的事情应该自己做主，不要老是依赖我们给你提意见。” 中国学生的父母对他们吼到：“放肆！翅膀长硬了是不是？敢把我的话当耳旁风？告诉你，就算你长出胡子，还是我们儿子，还得听我们的。” 美国教育体制和中国教育体制的区别 中国学校对孩子进行考试,目的是为了发现问题,淘汰之. 美国学校对孩子进行考试,目的是为了发现问题,改善之.
审阅签名： 版本/状态：D/1
Unit 5 ------ L2 ii. Having a free talk. 1. Make a big circle on the board. Write community inside the circle. Draw lines out from the circle and make four secondary circles. Label one of them lodging. Make lines form this circle to additional circles. Label these Hotels, Motels, and Hostels. 2. Ask students to close their books and help you complete the cluster. Use Medical Care, Parks and Recreation, and Residential Areas for the remaining three secondary circles. 3. In the Activity Bank CD-ROM template folder, there are cluster diagrams that can be duplicated for each student. ⅲ.Review some words. Introduction Identify well-know places in your community and ask students where they are located. Accept and answer. State the objective: Today we will give and follow street directions. Presentation 1 1.Write turn around on the board and ask students to repeat. 2.Ask students to open their books and look at the picture. Ask the questions in the box. ○A Practice the conversation. Ask volunteers to act out the conversation as if they are doing a role-play. Go over the new words briefly with them. ○B Practice these phrases with your classmates and teacher. Presentation 2 1.Study the map with students by asking questions. Such as: What street is next to First Street? Where is the car? 2.Review the direction vocabulary with the class again as you did in Exercise B on the previous page. 3.Draw a similar map on the board.
深圳特力吉盟投资有限公司 工程款审批与支付流程（草拟） 第一章总则 第一条为了规范工程款审批与支付制度, 严格控制公司资金的安排与使用，避免超付工程款现象发生，确保公司利益，针对工程款审批与支付的具体情况，制定本流程。 第二条凡属工程项目建设、安装、维修、装修等需要进行工程款支付、转账、抵扣等工作，均应遵守本流程。 第三条本流程所称工程款，是指资本性投入的工程项目中应支付给承包企业的工程承包款、甲供材料款、装修款、维修款及设备采购款、服务咨询费等。 第二章工程款支付规定 第四条办理工程项目建设、安装、维修、装修、甲供材料和设备采购等工程款支付业务，必须按照本流程及其他相关制度规定。 第五条签订工程合同要做到项目、合同、主体一一对应，即：一项目一合同，一合同一主体。 第六条工程合同签订时必须要有工程价款，签订的工程价款要有审定后的工程报价，审定报价应遵循“准确、谨慎、适度从严”的原则。 第七条施工过程中由于客观情况发生变化，必须变更合同内容的，应及时办理经济签证手续或签订补充合同，但新增工程内容原则上不纳入进度款支付范围。 第八条施工过程中产生的经济签证，原则上不允许支付工程进度款，待工程竣工结算完毕时进行一次性结算支付。 第九条严格按照合同约定主体进行工程款的支付。如承包人属企业法人单位，只能与合同主体单位办理前述相关业务。 第十条未签订合同前一律不得支付工程款。 第十一条设计工程部门应随时了解掌握工程进度，一般情况下（特别是土方、基坑支护、桩基等基础工程）做到完成一个分项工程，核定该部分工程量，开发成本部审核。即使暂时不能办理结算，也必须保管好实际完成工程量资料，以利后期结算、工程款支付。 第十二条与工程承包人和材料供应商签订的所有工程承包合同和材料供应合同必须报送一份完整合同原件到财务部备案。 第三章工程款支付审批程序 第十三条甲供材料设备审批程序 (一) 甲供材料设备供应商根据合同相关条款（如材料供应数量、质量、规格、供货时间等要求）填写《请款单》。 (二) 工程设计部现场代表按照合同条款和工地现场要求对供应商提供的实物进行验收，并填写《付款审批表》及验收意见（至少包含以下内容：实际收货数量、供货时间、货物质量及品名、种类、规格、型号是否与合同约定条件一致）。 (三)设计工程部、成本部负责人对《付款审批表》认真审查，核实后签署是否同意支付的明确意见，开发成本部分管总监签署审核意见。 (四) 财务部门对供应商出具的供货发票、实物验收单、供应合同及《付款审批表》的前期签审程序进行核实。同时，财务部门相关人员应对该供应商与本企业的往来账务（包括已付款、欠款金额等）进行核对、清理，若有欠款应及时扣回。审核完毕后财务
美国基础教育创新及启示 ——赴美培训考察的体会 (韩园林) 2006年3月3日 一流的校园环境 当一回演员 享受大家庭的温暖 当一回钳工 到州议会当一回议员 跟印地安人学钻木取火 2005年10月10日至12月30日,我作为深圳市教育系统赴美培训班第九期的48位成员之一,并作为班长带队前往美国进行了为期近三个月的学习考察,收获颇丰.在培训考察中,我切身感受到美国基础教育的特点,长处,特别是培养学生实践能力和创新意识的教学模式,鼓励学生自信,自主,个性,创新,给我留下了深刻的印象.他山之石,可以攻玉.考察归来,我就美国基础教育创新及启示作了思考. 一,美国教育现状:发达+创新 在美期间,我学习10周由艾登(Professor Adam Lee)教授执教的《西方教育模式》(Western Models of Instruction),由马丽老师执教的《班级管理》(Issure in Classroom Management);《education :introduction to teaching careers 》(教育学),其中《教育》由协和大学派教师在深圳成教学院讲授(内容主要包括美国教育史和西方教育哲学) 出席了8场专题讲座;参观了11所中小学,其中深入到8所学校听课并与这些学校的校长和老师交流对话;特别有趣的是参加了教育资源之行,参观了10所博物馆或教育中心;参观了美国哈佛,斯坦福等9所全美著名大学;饶有兴趣地感悟了万圣节,感恩节,圣诞节;最后是美国东部考察之行.行程数万里,纵横东西,走近美国的现代教育和文化生活. 1,美国教育简况 (1),美国学校体制 A.没有统一的国家教育体系,没有国家课程. B.联邦政府不办学校.
小学英语“有效教学”课堂教学模式 小学英语课堂教学常见课型分类 一、第一种分法：新授课与复习课 根据教材的整体结构与体例，小学三到六年级英语课课型主要分为新授课与复习课两大类。 二、第二种分法：词汇和句型教学课与课文教学课 每单元的BCD是词汇和句型教学课。A部分是课文教学课。 课文教学课分为会话式课文教学与语篇式课文教学两种。课文教学着重是培养学生的阅读理解能力和语言的综合运用能力。课文内容是针对某一话题的一篇长会话或一篇短文。课文中应用了一些新的词汇与句型，包含了一些语法和功能知识。 小学英语新授课基本课堂教学模式 按照英语新课程标准，小学英语课堂教学的基本模式是：热身活动——新知呈现——语言操练——综合运用——小结并布置作业。 1、热身/复习活动（Warming-up/Revision） 此环节的目的是：激活大脑和激活已学知识。把学生们的积极性调动起来，使他们积极参与到课堂学习中。 热身活动的形式主要包括：1、Sing some English songs（歌曲）.2、Say the poem or chant（歌谣）.3、Play some games（游戏）.4、TPR活动 5、Do the actions.（角色扮演）6、Greetings（问候）7、Free talk(问答交流或日常交流)8、Repeat the text(复述课文)等等。 注意活动的互动形式应为师生互动或生生互动。 2、新知呈现（Presentation） 新知呈现阶段是学生语言输入的最初阶段，是一节课的重点教学环节。 这阶段的教学原则是：（1）设置真实语境。（2）聚焦重点语言。（3）优选呈现方式。（4）体现短时高效。 新学习项目的呈现方式是非常重要的，呈现方式应当直观、生动有趣，能让学生一目了然，了解这堂课所要学习的语言知识。 呈现方式主要有：实物、图片、简笔画、挂图、课件、录音、游戏、歌曲、歌谣、表演、TPR等等。 3、语言操练（Practice） 语言操练阶段是学生学习和掌握语言的关键阶段，它起着承上启下的重要作用。 学生通过新知呈现阶段的学习，还需要大量的语言操练，以达到真正的语言
一、美国中小学品格教育面临的问题最近几十年来，越来越多的青年人由于没有意识到或漠视道德价值观念，而在不断地伤害自己或他人，这是美国社会的一个非常严重而且很急迫的问题。美国进行传统品格教育的机构，包括学校、社区、家庭和宗教组织在向青少年传授核心价值观念方面基本上没有什么效果。道德危机使美国社会的道德基础变得非常脆弱和不稳定。这此危机包括家庭破裂、贫困、种族不平等、隔离、愤世疾俗、新闻媒介中暴力与性的泛滥、实行主义以及贪婪等等。在美国，人们常常对个人权利比较关注，而不注意个人对家庭、社区以及国家应当承担的固有的义务和作为公民应尽的责任。尽管道德危机影响了美国社会的方方面面，但对于青少年却更具有极大的破坏作用。对于美国儿童来讲，应该成为其保护者和道德支柱的家庭本身就处于放任堕落之中，他们从来就没有一个应有的家庭，他们的邻里是一个充满恐怖的场所，街道是一个充斥暴力之地。美国儿童保护基金组织在1996年12月发表的年度报告中指出，美国现有近100万儿童无人照管甚至饱受凌辱和虐待，约50万儿童没有亲生父母照顾，而是被人领养，近1／7的儿童缺乏健康保险。近年来，由于家庭生活、教育和社会中存在的种族差别、贫富差别等方面的问题引起青少年吸毒、犯罪现象已经达到创记录水平。美国联邦调查局的一项报告说，1995年美国青少年因毒品犯罪而被捕的人数猛增到147万多人，比1990年增加一倍以上。冷漠、不信任、愤世疾俗和不诚实正在取代理想主义和乐观主义而成为解释青少年品格的名词。
二、美国公众对品格教育的支持及的成立品格教育日益得到美国公众的广泛理解和支持。尽管多数主要的教育团体反对在课堂上传播有关宗教信条，但同时又认为，传播为人们广泛接受的公民美德不仅是可能的，而且是非常有希望的。最近的一项盖洛普民意测验表明，60％的公众认为他们的社区会同意在公立学校进行一些基本的价值观念教育，90％多的公众支持公立学校向学生传授诚实97％、民主93％、对不同种族背景的美国人的接受93％、爱国主义91％、关心朋友和家庭成员91％以及道德勇气91％的观念、、1993,145。对于让学生培养一种较强的价值观念和伦理道德感的重要性的看法，来自美国学校管理者协会对学校领导人态度的综合报告显示，74％的学校领导人认为非常迫切；25％的领导人认为相当重要；只有1％的领导人认为不是很重要。同时还有70％的公众和51％的教师认为对于学校来说，向学生传授伦理道德观念比传授学术知识更重要。在此情况下，美国的品格教育协作组织简称于1992年3月成立了，1993年2月联合成为一个广泛的、无党派的、并自称是非盈利的各类组织和个人的联合体。她的主要任务是联络各地的品格教育组织，提供咨询服务，推广各地在品格教育方面好的做法和经验，影响国会和政府。在这一组织的推动下，美国国会已经通过法律，在全国12个州进行品格教育的试点工作。致力于培养青少年的公民美德和道德品格，以此作为创造一个更富有同情心和责任感的美国社会的一种途径。执行主任约翰·马丁先生说，希望与教育工作者和政策制定者合作，努力使品格教育成为公立学校的根本使命。
了解美国基础教育状况后的感想评 访美杂记(三)：殊途不同归──了解美国基础教育状况后的感想 刘凯湘(北京大学法学院教授） 因了富布赖特学者的身份，女儿琪琪得以当上了小小“留学生”，与我一同到了美国。我本未想带女儿前行，因为太太在国家机关工作，无法请一年的长假，我自己一人带着女儿，怕照顾不过来，但后来觉得对女儿来说这的确是一次很好的经历和体验，让她开开眼界，见见世面，所以最后还是把她带过来了。女儿在这里已经学习了快两个学期，我也因此通过与女儿交谈、辅导女儿的作业、看阅她们使用的教材、旁听她们的课堂教学、走访老师、参加学校组织的活动、查询与她的学习的相关资料等等，而对美国的中小学教学与教育以及与此相关的一些平时就比较关心的话题有了相对清楚的了解。当然，对教育制度尤其是中小学教育制度的看法和评价都有见仁见智的问题，好在女儿在这里待的时间不算太短，她所在的学校也是美国最典型的公立学校，我自己也对这个话题有一定程度的兴趣和关注，所以本文所言基本上从一个客观描述的角度着笔，但主观评价肯定也会较多地夹杂其中。 敞开的学校大门 我在来美之前通过网络查询到了我做访问学者的范登堡大学在Nashville市的具体位置，因为美国的公立中小学大体上也是按照学生的家庭住址统一安排就近入学的，当然，家庭附近的社区范围内可能有多所学校，你可以按自己的要求选择其中一所。我的目的是选一所离范登堡大学和离我们租的公寓最近的学校，当然同时我也得看看这所学校的其他情况，比如学生规模、历史、校园环境、接受入学的学生年级、课程设置等，最后选定了一所叫West End Middle School的学校，这所中学离范登堡大学约3公里，接受5－8年级的学生，女儿在国内刚刚小学毕业，现在上7年级（即初一）。确定学校后，我给该校负责办理学生入学事宜的校长助理写了一封邮件，告诉他我女儿的情况和我们准备到这所学校上学的打算。很快，接到了他的回信，首先对我女儿入学表示欢迎，然后告诉我们具体的手续如何办理。 到了美国，安顿好住宿后，我立刻带女儿前往学校办理手续。美国的中小学绝大多数在8月中下旬开学，少数在9月上旬开学，这所学校是8月20日开学的，他们已经开学快一个月了。我们到学校的办公室填写了几张表格，就算办妥了手续。第二天，女儿就上学去了。 我当时有点疑惑：我们在办理入学手续时，就只出示了我和女儿各自的护照，填写我在美国的访问学者身份，我在国内的工作单位和收入情况，在美国的住址，我作为监护人的联系方式，以及女儿的自然情况，未再要求我们出示任何别的证明，也不需要交纳任何费用，而且学校还为女儿当场办妥了免费午餐、免费校车、免费使用课本和教材、免费办理学生胸卡等手续，唯一要求补办的是女儿的疫苗记录，我忘了从国内带过来，而且补办期间不影响女儿上学。我当时就想：我们可是外国人啊，入学怎么这么简单，这么畅通无阻？我不禁就想起国内那些在大城市打工的“民工”，他们在城市有工作，有住址，他们都有中华人民共和国公民的身份证，但他们的子女却不能在他们工作的城市上学，或者要在经历了种种磨难甚至刁难、交纳了不菲的费用后才能获得入学资格，或者只能上那些专为“民工”举办的学校，