T h e ne w engl a nd jour na l o f medicine
Breast-Cancer Adjuvant Therapy
with Zoledronic Acid
Robert E. Coleman, M.B., B.S., M.D., Helen Marshall, M.Sc., David Cameron, M.B., B.S., M.D., David Dodwell, M.B., Ch.B., M.D.,
Roger Burkinshaw, B.Sc., Maccon Keane, M.D., Miguel Gil, M.D.,
Stephen J. Houston, M.B., B.S., M.D., Robert J. Grieve, M.B., Ch.B.,
Peter J. Barrett-Lee, M.B., B.S., M.D., Diana Ritchie, M.B., Ch.B., M.D., Julia Pugh, C.I.M.Dip., Claire Gaunt, B.Sc., Una Rea, B.Sc., Jennifer Peterson, B.App.Sc., Claire Davies, B.Sc., Victoria Hiley, B.Sc., Walter Gregory, Ph.D., and Richard Bell, M.B., B.S., for the AZURE Investigators*
The authors’ affiliations are listed in the Appendix. Address reprint requests to Dr. Coleman at the Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield S10 2SJ, United Kingdom, or at r.e.coleman@https://www.doczj.com/doc/b118792684.html,.
*Additional investigators in the Adjuvant Z oledronic Acid to Reduce Recurrence (AZURE) trial are listed in the Supple-mentary Appendix, available at NEJM .org.
This article (10.1056/NEJMoa1105195) was published on September 25, 2011, at https://www.doczj.com/doc/b118792684.html,.
N Engl J Med 2011;365:1396-1405. Copyright ? 2011 Massachusetts Medical Society.
Abstr act
Background
Data suggest that the adjuvant use of bisphosphonates reduces rates of recurrence and death in patients with early-stage breast cancer. We conducted a study to determine whether treatment with zoledronic acid, in addition to standard adjuvant therapy, would improve disease outcomes in such patients.
Methods
In this open-label phase 3 study, we randomly assigned 3360 patients to receive stan-dard adjuvant systemic therapy either with or without zoledronic acid. The zoledronic acid was administered every 3 to 4 weeks for 6 doses and then every 3 to 6 months to complete 5 years of treatment. The primary end point of the study was disease-free survival. A second interim analysis revealed that a prespecified boundary for lack of benefit had been crossed.
Results
At a median follow-up of 59 months, there was no significant between-group differ-ence in the primary end point, with a rate of disease-free survival of 77% in each group (adjusted hazard ratio in the zoledronic acid group, 0.98; 95% confidence in-terval [CI], 0.85 to 1.13; P = 0.79). Disease recurrence or death occurred in 377 patients in the zoledronic acid group and 375 of those in the control group. The numbers of deaths — 243 in the zoledronic acid group and 276 in the control group — were also similar, resulting in rates of overall survival of 85.4% in the zoledronic acid group and 83.1% in the control group (adjusted hazard ratio, 0.85; 95% CI, 0.72 to 1.01; P =0.07). In the zoledronic acid group, there were 17 confirmed cases of osteonecrosis of the jaw (cumulative incidence, 1.1%; 95% CI, 0.6 to 1.7; P <0.001) and 9 suspected cases; there were no cases in the control group. Rates of other adverse effects were similar in the two study groups.
Conclusions
These findings do not support the routine use of zoledronic acid in the adjuvant man-agement of breast cancer. (Funded by Novartis Pharmaceuticals and the National Can-cer Research Network; AZURE Current Controlled Trials number, ISRCTN79831382.)
Zoledronic Acid in Breast-Cancer Therapy
M etastasis is a complex process that is dependent on both the biologic fea-
tures of the primary tumor and cellular interactions within host tissues. In the bone micro-environment, cancer cells stimulate osteoblasts to release receptor activator of nuclear factor κB li-gand (RANKL), which binds to its receptor, RANK, on both precursor and mature osteoclasts. The resulting increase in osteoclastic bone resorption leads to the release of bone-derived growth factors that may provide a fertile environment for survival and growth of adjacent cancer cells.1 Thus, target-ing bone-cell function provides a potential addi-tional approach to preventing bone metastases as a component of standard adjuvant therapy.2 In many in vivo models, bisphosphonates prevent or delay metastasis.3 In addition, synergistic interactions between aminobisphosphonates and cytotoxic drugs have been shown in preclinical models.4,5 In patients with early-stage breast cancer, sev-eral clinical trials have suggested that the adjuvant use of bisphosphonates reduces rates of recurrence and death.6-8 In addition, despite a lack of regula-tory approval in most health care systems, the in-clusion of a bisphosphonate as part of adjuvant therapy has become increasingly widespread. In this randomized, controlled, open-label phase 3 study, called the Adjuvant Z oledronic Acid to Re-duce Recurrence (AZURE) trial, we evaluated the adjuvant use of zoledronic acid in a broad popu-lation of patients with stage II or III early-stage breast cancer.
Methods
Study Patients
The research protocol and statistical analysis plan are available with the full text of this article at https://www.doczj.com/doc/b118792684.html,. To be eligible for the study, all the pa-tients had to be at least 18 years of age, have a Karnofsky performance status of at least 80, and have a histologically confirmed breast cancer with axillary lymph-node metastasis (N1) or a T3–T4 primary tumor. Complete primary tumor resection was mandated or intended after neoadjuvant ther-apy. In addition, patients who were eligible for com-pletion surgery (margin excision, mastectomy, or axillary lymph-node dissection) after completion of adjuvant chemotherapy could be included. Patients were not eligible if there was clinical or imaging evidence of distant metastases or if com-plete treatment of the primary breast tumor and regional lymph nodes was not possible. Other ex-clusion criteria included a cancer diagnosis within the preceding 5 years, use of bisphosphonates dur-ing the previous year, or a diagnosis of osteoporo-sis or other bone disease likely to require bone-targeted treatment. The serum creatinine level had to be less than 1.5 times the upper limit of the normal range. In 2005, after case reports of os-teonecrosis of the jaw associated with bisphospho-nates,9an amendment was adopted to exclude patients with clinically significant, active dental problems or planned jaw surgery.
Randomization and Treatment
After providing written informed consent, patients were randomly assigned in a 1:1 ratio to receive standard adjuvant systemic therapy (control group) or standard adjuvant systemic therapy along with zoledronic acid. The zoledronic acid was admin-istered immediately after each cycle of adjuvant chemotherapy in a 4-mg dose by intravenous infu-sion every 3 to 4 weeks for 6 cycles and then every 3 months for 8 doses, followed by 5 cycles on a 6-month schedule for a total of 5 years. Dose ad-justments for renal-function abnormalities were recommended in accordance with the product li-cense. Daily oral supplements containing calcium (400 to 1000 mg) and vitamin D (200 to 500 IU) were recommended for all patients during the first 6 months and were continued thereafter at the dis-cretion of the treating physician.
External-beam radiotherapy to the breast and chest wall, with or without irradiation of regional lymph nodes, and adjuvant cytotoxic and endocrine treatments were given in accordance with standard protocols at each participating institution. After regulatory approval of trastuzumab for adjuvant use, the drug was allowed in patients with HER2-positive tumors.
To minimize imbalances in tumor and treat-ment characteristics between the study groups, the central, automated, 24-hour, computer-generated telephone randomization system incorporated the following variables: the number of involved axillary lymph nodes, clinical tumor stage, estrogen-recep-tor status, type and timing of systemic therapy, menopausal status, statin use or nonuse, and study center.
Prerandomization investigations in accordance with institutional protocols included histologic confirmation of breast cancer; testing of hemato-logic, renal, and hepatic function; and imaging
T h e ne w engl a nd jour na l o f medicine
for the purpose of tumor staging. The follow-up schedule for both the zoledronic acid group and the control group included clinical assessment, physical examination, monitoring for adverse events, and measurement of hematologic, renal, and hepatic function. Investigations for possible recurrence were clinically directed as deemed ap-propriate by the treating physician. Routine follow-up imaging was not mandated.
The study treatment was discontinued in the event of a distant recurrence, unacceptable toxic-ity, three consecutively missed treatments, the pa-tient’s request, the treating physician’s recom-mendation, or completion of 5 years of treatment. Continuation of the study medication was recom-mended in the event of a locoregional recurrence and at the physician’s discretion after the diagno-sis of a new primary cancer.
Study End Points
The primary end point of the study was disease-free survival, which was defined as an absence of dis-tant recurrence, of any invasive locoregional recur-rence (except for ipsilateral operable relapse within a conserved breast), and of death from any cause without recurrence. The secondary end point was overall survival. Prespecified subgroup analyses were based on variables included in the random-ization.
We also performed exploratory analyses to in-vestigate treatment effects on sites of first recur-rence. After a protocol amendment was approved before the first interim analysis in 2008, we added another secondary end point: invasive-disease –free survival, which was defined according to the Stan-dardized Definitions for Efficacy and End Points in Adjuvant Breast Cancer Trials (STEEP) guidelines.10 (A complete definition is provided in the Supple-mentary Appendix, available at https://www.doczj.com/doc/b118792684.html,.) The date of recurrence was defined as the date on which relapse was first suspected, rather than the date on which it was confirmed, to reduce the risk of ascertainment bias. On-site and telephone-based monitoring was performed to ensure that recur-rence dates were backdated to the date on which the event was first suspected, when this date preceded clinical, histologic, or imaging confir-mation.11
Study Oversight
The study was sponsored by the University of Sheffield and approved as a United Kingdom na-tional trial by the Clinical Trials Advisory Awards Committee. Grant support was provided by No-vartis Pharmaceuticals and was supplemented in the United Kingdom by the infrastructure of the National Cancer Research Network. Novartis Pharmaceuticals donated study supplies of zole-dronic acid. The authors developed the study con-cept, wrote the protocol, and performed and re-viewed all analyses. The study was conducted in accordance with the protocol, with amendments to reduce the risk of osteonecrosis of the jaw and to inform both patients and dental practi-tioners of this risk. The first author wrote the first draft of the manuscript, and all authors were involved in revision and approval of the manuscript. Novartis Pharmaceuticals was given an opportunity to comment on the manuscript, but all decisions on submission of the manu-script for publication were made by the authors and the trial steering committee.
Statistical Analysis
A final analysis was planned after the primary end point (disease-free survival) had occurred in 940 patients, on the basis of the recruitment of 3300 patients during a 3-year period, an anticipat-ed rate of disease-free survival of 75% at 3 years, and a 5% annual rate of loss to follow-up. It was estimated that these numbers would provide a power of 80% to detect a relative reduction of 17% in the rate of disease recurrence or death among patients receiving zoledronic acid, at a two-sided level of significance of 0.05, which would approx-imate an absolute benefit of 3.7 percentage points.
A single interim analysis was planned after the primary end point had been reached in 470 pa-tients, with a two-sided alpha level of 0.005.12 After this analysis was performed, on the advice of the independent data and safety monitoring committee, no efficacy data were released. Be-cause the rate of events contributing to the pri-mary end point was lower than predicted (result-ing in a combined rate of disease-free survival of 85% at 3 years), an independent statistician who was unaware of the findings and was not in-volved in the first interim analysis provided re-vised stopping boundaries for both efficacy and lack of benefit that would allow timely release of a clinically important result. A second inter-im analysis was planned after the primary end point had occurred in at least 705 patients, along with a 0.5% probability of declaring false positive results (one-sided) or a 5.0% probability of de-claring negative results with the use of a group
Zoledronic Acid in Breast-Cancer Therapy
sequential-design method.13 The analysis was car-ried out on 752 events, resulting in an efficacy boundary for the hazard ratio of 0.833 (lower boundary) and a lack-of-efficacy boundary of 0.936 (upper boundary). At this interim analy-sis, the lack-of-efficacy boundary was crossed, and the committee recommended the release of results.
We used Kaplan–Meier survival curves to eval-uate the rates of disease-free survival, invasive-disease –free survival, and overall survival. We compared between-group differences using the log-rank test and a Cox proportional-hazards model to adjust for the minimization factors (ex-cluding study center). We calculated rates of osteo-necrosis of the jaw using cumulative incidence functions, in which deaths without a diagnosis of osteonecrosis of the jaw were considered to be competing-risk events and were compared with the use of the log-rank test. In a subgroup analy-sis, we used the Cox proportional-hazards model to adjust for statistically significant factors in the overall analysis (estrogen-receptor status, lymph-node involvement, and tumor stage).
All adverse events were evaluated in the safety population. No statistical testing was carried out on these end points, apart from confirmed cases of osteonecrosis of the jaw, since this disorder had been identified a priori as a clinically impor-tant event linked to bisphosphonate use. All analy-ses were performed with the use of SAS software, version 9.2 (SAS Institute).
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R esults
Study Patients
Between September 2003 and February 2006, a total of 3360 eligible women from 174 centers in seven countries were recruited. Of these patients, 1681 were assigned to the zoledronic acid group and 1679 to the control group. Among the patients assigned to receive zoledronic acid, 1665 (99.0%) received at least one dose (Fig. 1). The tumor and treatment characteristics of the patients in the two study groups were well balanced (Table 1). A total of 95.5% of the patients received chemotherapy, which was planned to include an anthracycline in 97.6% of the patients and a taxane in 24.2%; 208 patients received neoadjuvant chemotherapy and 3000 received postoperative chemotherapy. When the database was locked, on October 18, 2010, the median follow-up period was 59.3 months (interquartile range, 53.5 to 60.9) in the zoledronic acid group and 58.6 months (interquartile range, 52.7 to 60.9) in the control group. The median time since the last follow-up contact for all surviving patients was 5.9 months (interquartile range, 3.8 to 9.1), which was identical in the two groups.
Primary and Secondary End Points
At 5 years, 76.9% and 77.1% of the patients in the treatment and control groups, respectively, were alive and disease-free; 377 patients in the zoledronic acid group and 375 patients in the control group had recurrent disease or had died (adjusted hazard ratio in the zoledronic acid group, 0.98; 95% confi-dence interval [CI], 0.85 to 1.13; P =0.79) (Fig. 2A). Similarly, at 5 years, 75.4% and 75.3% of the pa-tients in the treatment and control groups, re-spectively, were alive and free of invasive disease; 404 patients in the zoledronic acid group and 403 patients in the control group had invasive disease or had died (adjusted hazard ratio, 0.98; 95% CI, 0.85 to 1.12; P = 0.73) (Fig. 2B). The dis-tributions of invasive-disease events were also similar in the two groups; 65.8% were distant recurrences, of which 230 were in bone (108 in the zoledronic acid group and 122 in the control group) (Table 1 in the Supplementary Appendix). Despite the known effects of many cancer treatments on bone health and the risk of osteo-porosis, only 146 patients in the control group (8.7%) received a bisphosphonate before reach-ing the primary end point. To date, 519 patients have died: 243 in the zoledronic acid group (5-year overall survival rate, 85.4%) and 276 in the control group (5-year overall survival rate, 83.1%) (adjusted hazard ratio with zoledronic acid, 0.85; 95% CI, 0.72 to 1.01; P = 0.07).
Subgroup Analyses
Prespecified subgroup analyses showed a consis-tent lack of differential effect across the variables that were included in the randomization, with the
* There were no significant differences between the two groups.
Zoledronic Acid in Breast-Cancer Therapy exception of menopausal status. Significant hetero-
geneity of treatment effect (χ21= 7.91, P = 0.005)
on the rate of invasive-disease –free survival was
observed between patients who had undergone
menopause more than 5 years earlier and all
other patients (those who were premenopausal or
perimenopausal and those with unknown meno-
pausal status). At 5 years, among postmenopausal
patients, the rates of invasive-disease –free survival
were 78.2% in the zoledronic acid group and 71.0%
in the control group (adjusted hazard ratio with
zoledronic acid, 0.75; 95% CI, 0.59 to 0.96; P = 0.02);
among all other patients, the rates were 74.1% in
the zoledronic acid group and 77.2% in the control
group (adjusted hazard ratio, 1.15; 95% CI, 0.97 to
1.36; P = 0.11) (Fig. 3A and 3B). In addition, among
patients who had undergone menopause more than
5 years earlier, the 5-year overall survival rate was
84.6% in the zoledronic acid group and 78.7% in
the control group (adjusted hazard ratio, 0.74;
95% CI, 0.55 to 0.98; P = 0.04), as compared with
all other patients, for whom the rates were 85.7%
in the zoledronic acid group and 85.1% in the con-
trol group (adjusted hazard ratio, 0.97; 95% CI,
0.78 to 1.21; P = 0.81) (Fig. 3C and 3D). These dif-
ferences were independent of estrogen-receptor
status, tumor stage, and lymph-node involvement.
With respect to distant skeletal recurrence,
the effects of zoledronic acid did not differ sig-
nificantly between the two menopausal groups
(χ21=0.14, P =0.70). In contrast, for the other com-
ponents of invasive-disease –free survival, there
was a consistent, significant difference in the ef-
fects of zoledronic acid according to menopaus-
al status, with an apparent benefit in postmeno-
pausal women and potential harm in all other
women (χ21= 14.00, P<0.001) (Fig. 1 in the Sup-
plementary Appendix).
Adverse Events
Dental adverse events were more frequent in the
zoledronic acid group than in the control group,
and investigators reported 26 cases of osteonecro-
sis of the jaw. Of these cases, 17 were confirmed on
central review, all in the zoledronic acid group
(rate, 1.1%; 95% CI, 0.6 to 1.7), including 3 cases occurring after metastases to bone. Of the 9 un-confirmed cases, 4 did not conform to a standard definition of osteonecrosis of the jaw, and further information is awaited on 5 cases. The rate of frac-ture was reduced in patients receiving zoledronic acid, with 175 fractures (65 in the zoledronic acid group and 110 in the control group) in 152 patients (60 in the zoledronic acid group and 92 in the control group). Rates of other adverse events were similar in the two study groups (Table 2, and Ta-bles 2 and 3 in the Supplementary Appendix). Most serious adverse events were related to che-motherapy or other cancer treatments. No sig-nificant difference was seen in rates of neutro-
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penic fever. Chemotherapy dose reductions and delays were similar in the two study groups (data not shown).
Discussion
Clinical trials of adjuvant bisphosphonates in pa-tients with early-stage breast cancer have had variable results. A reduction in bone metastases and improved overall survival were reported in two trials of oral clodronate.6,7 However, two other trials showed no benefit.14,15 More recently, in the Austrian Breast and Colorectal Cancer Study Group 12 (ABCSG-12) trial (https://www.doczj.com/doc/b118792684.html, num-ber, NCT00295646) involving 1803 premenopausal women with estrogen-receptor–positive breast
Zoledronic Acid in Breast-Cancer Therapy
cancer who were treated with goserelin and ei-ther tamoxifen or anastrozole, the administration of zoledronic acid every 6 months for 3 years re-duced the risk of disease recurrence by about one third.8 In addition, several large randomized tri-als addressing the question have completed ac-crual and are in the follow-up phase.
In our study, no improvement was seen in the rate of disease-free survival, the primary end point of the study; rates of invasive-disease–free survival and overall survival were similar in the two study groups. This primary result is unlikely to change with further follow-up and appears to differ mark-edly from the findings of Gnant and colleagues in the ABCSG-12 study.8 However, there are im-portant differences between the two study popu-lations. In the ABCSG-12 study, all the patients started receiving goserelin and endocrine therapy (resulting in a rapid suppression of reproductive hormones) before the initiation of bisphosphonate treatment; in addition, the patients had disease with a good prognosis, and less than 5% received chemotherapy. In contrast, the premenopausal pa-tients in our study had a less favorable prognosis, more than 95% received chemotherapy, and all had premenopausal levels of reproductive hormones at study entry. Only three of the premenopausal patients (0.2%) in our study received goserelin. In a prespecified analysis, our finding of a possible benefit of zoledronic acid in patients who had undergone menopause more than 5 years before study entry is intriguing. From an endo-crine perspective, the postmenopausal patients in our study were similar to the goserelin-treated patients in the ABCSG-12 study,8who had low levels of reproductive hormones at study entry. The curves for rates of disease-free survival in the postmenopausal subgroup diverged rapidly (absolute difference, 3 percentage points at 1 year and 5 percentage points at 2 years) and showed a small but significant survival advantage for patients who received zoledronic acid. Further-more, the use of zoledronic acid appeared to have divergent effects on metastasis to visceral and locoregional sites according to menopausal status. Our analysis of the interaction of the various components of invasive-disease–free sur-vival suggests a systemic effect of zoledronic
* Listed are serious adverse events that occurred in more than 1% of patients in either study group in the safety popula-tion, which is defined in the Supplementary Appendix. Adverse events that have been classified according to organ sys-tem and grade are listed in Tables 2 and 3 in the Supplementary Appendix. NA denotes not applicable.
? Positive values indicate a greater frequency of the event in the zoledronic-acid group. Between-group differences were calculated before the rounding of percentages.
? In addition to the cases of pulmonary embolus that were classified as serious adverse events, 3 cases (1 in the zole-dronic-acid group and 2 in the placebo group) were reported as adverse events, for a total of 41 patients with pulmo-nary embolus (1.5% in the zoledronic acid group and 0.9% in the control group; absolute difference, 0.6 percentage points; 95% confidence interval, -0.1 to 1.4).
§ P<0.001.
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acid that operates differently according to meno-pausal status and that is distinct from any effect in bone (Fig. 1 in the Supplementary Appendix). The explanation for this finding is unclear, but perhaps bone provides a sanctuary for cancer cells, and after treatment with zoledronic acid, the ability of cancer cells to disseminate to other body sites is dependent on the presence of reproductive hormones.
The apparent early benefits seen in the post-menopausal subgroup suggest that the initial phase of treatment, when zoledronic acid is com-bined with chemotherapy, may be most impor-tant. During neoadjuvant chemotherapy with zole-dronic acid, an increased tumor response in the breast16 and a reduced number of disseminated tumor cells in the bone marrow17 have been ob-served, suggesting positive interactions between zoledronic acid and chemotherapy.
Adjuvant chemotherapy would be expected to induce menopause in a high proportion of women over the age of 40 years. However, it may take many months for chemotherapy to affect reproductive hormone levels, and despite causing amenorrhea, chemotherapy may not result in complete ovar-ian suppression. It is unclear how the endocrine environment in bone might influence interactions between chemotherapy and zoledronic acid. How-ever, as levels of ovarian-derived inhibin decline after menopause, the control of bone-cell function changes from primary regulation through effects of inhibins on osteoblasts to control by locally produced activin interacting with bone morpho-genic proteins and noggin to drive bone turnover.18 In our study, zoledronic acid had no demon-strable effect on chemotherapy-associated toxic effects. A full description of the adverse-event profile in this trial has been reported previous-ly.19 Confirmed osteonecrosis of the jaw occurred in 1.1% of patients who were treated with zole-dronic acid, with an additional nine suspected cases. Resolution of osteonecrosis of the jaw was seen in some cases, but the observed frequency of this complication in our study was higher than that reported in other studies of zoledronic acid in patients receiving adjuvant therapy.8,20 This discrepancy presumably reflects the more intensive schedule of zoledronic acid and greater use of chemotherapy in our study. On the positive side, zoledronic acid was associated with a re-duction in rates of fracture, particularly among patients who had a disease recurrence.
In conclusion, our findings do not support the routine use of zoledronic acid as adjuvant ther-apy in unselected patients with early-stage breast cancer. Further investigation into the possible in-teraction between zoledronic acid and reproduc-tive hormones is required. For postmenopausal women, the use of bisphosphonates remains ap-propriate for the prevention of treatment-induced bone loss and osteoporosis and might have bene-ficial effects on disease outcomes. The optimum schedule, duration, and type of bisphosphonate therapy remain unknown.
Supported by a grant from Novartis Pharmaceuticals and by the National Cancer Research Network.
Disclosure forms provided by the authors are available with the full text of this article at https://www.doczj.com/doc/b118792684.html,.
We thank the patients who took part in this trial; all inves-tigators and research staff at the 174 recruiting centers; the staff at the clinical trials research units in the United Kingdom (Clinical Trials Research Unit [CTRU], University of Leeds; In-stitute of Cancer Research [ICR], Sutton; Edinburgh Clinical Trials Unit; and Cancer Research U.K. Clinical Trials Unit, Uni-versity of Birmingham), Australia (Victorian Cooperative Oncol-ogy Group), Ireland (Irish Clinical Oncology Research Group), and Spain (Spanish Group of Treatment Study and Other Expe-riences in Solid Tumors); Michelle Collinson (CTRU) and Rog-er A’Hern (ICR) for their statistical input; the members of the trial steering committee under the chairmanship of Prof. Mat-thew Seymour; and the members of the independent data and safety monitoring committee (Dr. Laurence Collette, Prof. Mal-colm Mason, and Dr. Richard Theriault).
Appendix
The authors’ affiliations are as follows: the Academic Unit of Clinical Oncology, Weston Park Hospital, University of Sheffield (for the National Cancer Research Network and National Institute for Health Research) (R.E.C., R. Burkinshaw); Clinical Trials Research Unit (H.M., C.D., V.H., W.G.) and St. James Institute of Oncology (D.D.), University of Leeds, Leeds; Western General Hospital, University of Edinburgh, Edinburgh (D.C.); St. Luke’s Cancer Centre, Royal Surrey County Hospital, Guildford (S.J.H.); University Hospitals Coventry and Warwickshire National Hospital Service Trust, Coventry (R.J.G.); Velindre Cancer Center, Whitchurch, Cardiff (P.J.B.-L.); Beatson West of Scotland Cancer Centre, Glasgow (D.R.); Institute of Cancer Research Clinical Trials Support Unit, Sutton (J.P.); Cancer Research United Kingdom Clinical Tri-als Unit, University of Birmingham, Birmingham (C.G.); and Cancer Clinical Trials Team, National Health Service National Services Scotland, Edinburgh (U.R.) — all in the United Kingdom; University Hospital Galway, Galway, Ireland (for the All Ireland Cooperative Oncology Research Group) (M.K.); Institut Català d’Oncologia–Institut d’Investigació Biomèdica de Bellvitge, L’Hospitalet de Llobregat, Barcelona (for the Spanish Group of Treatment Study and Other Experiences in Solid Tumors) (M.G.); and Victoria Cooperative Oncology Group, Cancer Council Victoria, Carlton (J.P.); and Andrew Love Cancer Centre, Geelong (for the Victoria Cooperative Oncology Group) (R. Bell) — both in Australia.
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References
解读国家税务总局公告2011年第13号：纳税人资产重组不缴增值税 来源：中国财务总监网近日，国家税务总局下发了《关于纳税人资产重组有关增值税问题的公告》（国家税务总局公告2011年第13号）（以下简称“13号公告”），就纳税人资产重组有关增值税问题公告如下：纳税人在资产重组过程中，通过合并、分立、出售、置换等方式，将全部或者部分实物资产以及与其相关联的债权、负债和劳动力一并转让给其他单位和个人，不属于增值税的征税范围，其中涉及的货物转让，不征收增值税。至此，关于资产重组涉及的增值税如何缴纳有了明确政策界定，之前的争议就此画上句号。笔者认为，这个政策是国家鼓励纳税人进行资产重组一个很重要的利好政策。 企业合并重组不缴增值税 按照《公司法》的规定，一个公司吸收其他公司为吸收合并，被吸收的公司解散。两个以上公司合并设立一个新的公司为新设合并，合并各方解散。公司合并时，合并各方的债权、债务，应当由合并后存续的公司或者新设的公司承继。公司合并重组时，一方的资产要过户给另一方，资产的所有权属发生转移，是否缴纳增值税呢？13号公告之前，政策上主要依据的是《国家税务总局关于转让企业全部产权不征收增值税问题的批复》（国税函﹝2002﹞420号），该文件就江西省国税局《关于江西省电力公司转让上犹江水电厂全部产权是否征收增值税问题的请示》批复如下：根据《中华人民共和国增值税暂行条例》及其实施细则的规定，增值税的征收范围为销售货物或者提供加工、修理修配劳务以及进口货物。转让企业全部产权是整体转让企业资产、债权、债务及劳动力的行为，因此，转让企业全部产权涉及的应税货物的转让，不属于增值税的征税范围，不征收增值税。虽然文件规定转让企业全部产权不征收增值税，但江西省国税局请示的问题是主管单位将下属单位转让的行为，该政策答复是否广泛适用各类企业合并重组存在争议。 根据13号公告规定，由于企业合并中一方或双方均要注销，注销后的企业其资产、债权、债务及劳动力随之转移，因此，企业合并不属于增值税征税范围，不缴纳增值税。 部分企业分立重组不缴增值税
国家税务总局2011年第24号关于非居民企业所得税管理若干问题的公告依据《中华人民共和国企业所得税法》及其实施条例（以下简称企业所得税法），现就非居民企业所得税管理有关问题公告如下： 一、关于到期应支付而未支付的所得扣缴企业所得税问题 中国境内企业（以下称为企业）和非居民企业<1>签订与利息、租金、特许权使用费等所得<2>有关的合同或协议，如果未按照合同或协议约定的日期支付上述所得款项，或者变更或修改合同或协议延期支付，但已计入企业当期成本、费用，并在企业所得税年度纳税申报中作税前扣除的，应在企业所得税年度纳税申报时按照企业所得税法有关规定代扣代缴企业所得税。<3> 如果企业上述到期未支付的所得款项，不是一次性计入当期成本、费用，而是计入相应资产原价或企业筹办费，在该类资产投入使用或开始生产经营后分期摊入成本、费用，分年度在企业所得税前扣除的, 应在企业计入相关资产的年度纳税申报时就上述所得全额代扣代缴企业所得税。 如果企业在合同或协议约定的支付日期之前支付上述所得款项的, 应在实际支付时按照企业所得税法有关规定代扣代缴企业所得税。 <1>非居民企业是否包括依照外国（地区）法律成立且实际管理机构不在中国境内，但在中国境内设立机构、场所的非居民企业？如办事处、代表机构。 <2>所得是否还包括承担工程作业、提供劳务和转让财产两项所得？国税发[2009]3号国家税务总局关于印发《非居民企业所得税源泉扣缴管理暂行办法》的通知第三条、第七条有相关的规定。 <3>是对条例18、19、20、23条收入确认时间的特殊规定。 二、关于担保费税务处理问题 非居民企业<4>取得来源于中国境内的担保费，应按照企业所得税法对利息所得规定的税率<5>计算缴纳企业所得税。上述来源于中国境内的担保费，是指中国境内企业、机构或个人在借贷、买卖、货物运输、加工承揽、租赁、工程承包等经济活动中，接受非居民企业提供的担保所支付或负担的担保费或相同性质的费用。 <4>是否包括在中国境内设立的机构、场所的非居民企业？ <5>是对财税字[1998]001号国家税务总局关于外国企业来源于中国境内的担保费所得税务处理问题的通知的修正,类似规定国税发[2009]2号国家税务总局关于印发《特别纳税调整实施办法（试行）》的通知第八十七条，是否可以享受协定规定的优惠税率？如何理解国税发[2010]75号国家税务总局关于印发《〈中华人民共和国政府和新加坡共和国政府关于对所得避免双重征税和防止偷漏税的协定〉及议定书条文解释》的通知，对于与利息相关的其他所得是否应属于“利息”的范畴，应根据其性质区别对待：2.与贷款业务相关的并附属于债权的所得可认定为利息，对独立发生于债权方以外的，如单独收取的担保费等，原则上不应认定为利息。 三、关于土地使用权转让所得征税问题
关于国家安全生产监督管理总局公告2014年第13号《危险化学品生产、储存装置个人可接受风险标准和社会可接受风险标准（试行）》中的“我国个人可接受风险标准值表”与国家安全生产监督管理总局令第40号《危险化学品重大危险源监督管理暂时规定》附件2可容许风险标准中的“表1可容许个人风险标准”在安全评价执行过程中存在的有关疑惑 在国家安全生产监督管理总局2014年第13号公告《危险化学品生产、储存装置个人可接受风险标准和社会可接受风险标准（试行）》解读中明确指出：“本次将定量风险评价应用于外部安全防护距离的确定，是在《化工企业定量风险评价导则》（AQ/T 3046-2013）公布以后，对国家安全生产监督管理总局40号令第九条有关规定的扩展延伸”，那么在《危险化学品生产、储存装置个人可接受风险标准和社会可接受风险标准（试行）》中规定的我国个人可接受风险标准值表（以下简称个人可接受风险标准）规定的“防护目标”是否可以认为是对安监总局40号令附件2《可容许风险标准》中“表1可容许个人风险标准中”（以下简称可容许个人风险标准）“危险化学品单位周边重要目标和敏感场所类别”的补充和延伸解释？ 由于二者存在不一致之处，在具体的安全评价（评估）执行过程中有关评价单位之间包括评审专家在内存在诸多分歧，影响到标准的宣贯执行，为便于理解，首先列出上述两个标准对比如下： 我国个人可接受风险标准值表 （安监总局2014年第13号公告 2014年5月7日）
可容许个人风险标准 （安监总局令第40号附件2可容许风险标准，2011年12月1日起施行）
从上表可以看出，二者在外部防护对象定义（分别为防护目标与危险化学品单位周边重要目标和敏感场所类别举例）及标准等级与数值上（如三级风险与二级风险、人口数量确定等）有诸多不同之处，执行中存在疑惑，具体表现为： 1、《个人可接受风险标准》对于新建装置人员个体容许死亡概率≤3×10-7中规定的“高敏感场所”举例比《可容许个人风险标准》增加了“监狱”，该增加项是否适用于《可容许个人风险标准》中个体容许死亡概率＜3×10-7中关于“高敏感场所”的举例规定？《个人可接受风险标准》“重要目标”举例增加了“军事禁区”，没有“党政机关”，请问：“党政机关”是否适用于《个人可接受风险标准》，军事禁区是否适用于《可容许个人风险标准》？在《个人可接受风险标准》中“特殊高密度场所”规定（人数≥100人）而且举例除“大型体育场、大型交通枢纽”外，另外增加了“露天市场、居民区、宾馆、度假村、办公场所、商场、饭店、娱乐场所”，请问：（人数≥100人）之规定以及举例中的几个增加项是否适用于《可容许个人风险标准》，如果不适用，在40号令执行时人数规模有无其它参考规定？ 2、在《个人可接受风险标准》中对于新建装置人员个体容许死亡（概率 ≤3×10-6）规定的“居住类高密度场所”和“公众聚集类高密度场所”列举的内容与《可容许个人风险标准》中关于人员个体容许死亡概率＜1×10-6中规定的“居住类高密度场所”和“公众聚集类高密度场所”完全一致，但是《个人可接受风险标准》中规定了人口规模（30人≤人数＜100人），请问该人数规定是否适用《可容许个人风险标准》，还是另有人数规模规定？ 3、《危险化学品生产、储存装置个人可接受风险标准和社会可接受风险标准（试行）》解读中指出“与40号令第九条规定相比，采用定量风险评价法确定外部安全防护距离的装置范围更广，依据的个人可接受风险标准更适用于危险性稍低于40号令第九条所列的装置。因此当危化装置符合40号令第九条规定的情形，
国家税务总局公告2011年第40号关于增值税纳税义务发生时间有关问题的公告<附解> (2011-08-16 10:41:24) 转载 标签：增值税 国家税务总局 公告 2011年 40号 财经 解读分类：2011国家税务总 局公告 国家税务总局 关于增值税纳税义务发生时间有关问题的公告 国家税务总局公告2011年第40号成文日期：2011-07-15 根据《中华人民共和国增值税暂行条例》及其实施细则的有关规定，现就增值税纳税义务发生时间有关问题公告如下： 纳税人生产经营活动中采取直接收款方式销售货物，已将货物移送对方并暂估销售收入入账，但既未取得销售款或取得索取销售款凭据也未开具销售发票的，其增值税纳税义务发生时间为取得销售款或取得索取销售款凭据的当天；先开具发票的，为开具发票的当天。 本公告自2011年8月1日起施行。纳税人此前对发生上述情况进行增值税纳税申报的，可向主管税务机关申请，按本公告规定做纳税调整。 特此公告。
国家税务总局 二○一一年七月十五日分送：各省、自治区、直辖市和计划单列市国家税务局、地方税务局。 ————————————————————————————————————————————————— <原创>解释： 注意：采取直接收款方式销售货物的形式下适用此公告规定，其他方式下不适用此公告。 一、“采取直接收款方式销售货物”新旧差异。 旧：采取直接收款方式销售货物，不论货物是否发出，均为收到销售款或者取得索取销售款凭据的当天； 新：采取直接收款方式销售货物，已将货物移送对方并暂估销售收入入账，但既未取得销售款或取得索取销售款凭据也未开具销售发票的，其增值税纳税义务发生时间为取得销售款或取得索取销售款凭据的当天；先开具发票的，为开具发票的当天。 理解：“已将货物移送对方并暂估销售收入入账”，以下情况不需进行增值税纳税申报： （一）未取得销售款； （二）未取得索取销售款凭据； （三）未开具销售发票。 二、取得索取销售款凭据的当天，“销售款凭据”具体是指什么？ 答：可以理解为提货单.验收单.入库单.合同.发票的组合。[山东国税]
国家税务总局 关于调整增值税即征即退优惠政策管理措施有关问题的公告 国家税务总局公告2011年第60号 为加快退税进度，提高纳税人资金使用效率，扶持企业发展，税务总局决定调整增值税即征即退企业实施先评估后退税的管理措施。现将有关问题公告如下： 一、将增值税即征即退优惠政策的管理措施由先评估后退税改为先退税后评估。 二、主管税务机关应进一步加强对即征即退企业增值税退税的事后管理，根据以下指标定期开展纳税评估。 （一）销售额变动率的计算公式： 1.本期销售额环比变动率＝（本期即征即退货物和劳务销售额-上期即征即退货物和劳务销售额）÷上期即征即退货物和劳务销售额×100％。 2.本期累计销售额环比变动率＝（本期即征即退货物和劳务累计销售额-上期即征即退货物和劳务累计销售额）÷上期即征即退货物和劳务累计销售额×100％。 3.本期销售额同比变动率＝（本期即征即退货物和劳务销售额-去年同期即征即退货物和劳务销售额）÷去年同期即征即退货物和劳务销售额×100％。 4.本期累计销售额同比变动率＝（本期即征即退货物和劳务累计销售额-去年同期即征即退货物和劳务累计销售额）÷去年同期即征即退货物和劳务累计销售额×100％。 （二）增值税税负率的计算公式 增值税税负率＝本期即征即退货物和劳务应纳税额÷本期即征即退货物和劳务销售额×100％。 三、各地可根据不同的即征即退项目设计、完善评估指标。主管税务机关通过纳税评估发现企业异常情况的，应及时核实原因并按相关规定处理。 四、本公告自2011年12月1日起施行。《国家税务总局关于增值税即征即退实施先评估后退税有关问题的通知》（国税函[2009]432号）同时废止。 特此公告。 国家税务总局 二○一一年十一月十四日 根据国务院常务会议精神，将于明年开展的深化增值税制度改革试点包括三个方面的具体内容：第一，先在上海市交通运输业和部分现代服务业等开展试点，条件成熟时可选择部分行业在全国范围进行试点。第二，在现行增值税17%标准税率和13%低税率基础上，新增11%和6%两档低税率。第三，试点期间原归属试点地区的营业税收入，改征增值税后收入仍归属试点地区。试点行业原营业税优惠政策可以延续，并根据增值税特点调整。纳入改革试点的纳税人缴纳的增值税可按规定抵扣。
中华人民共和国财政部公告2011年第18号 来源：财政部新闻办公室发布时间：2011-04-16 中华人民共和国财政部公告2011年第18号 根据国家国债发行的有关规定，财政部决定发行2011年记账式贴现(一期)国债(以下简称本期国债)，现将有关事项公告如下： 一、本期国债通过全国银行间债券市场和证券交易所市场(以下简称各交易场所)面向社会各类投资者发行。 二、本期国债计划发行面值100亿元，实际发行面值为100亿元。 三、本期国债期限91天，经招标确定的发行价格为99.383元，折合年收益率为2.55％，本期国债2011年4月18日开始发行并计息，4月20日发行结束。4月22日起，本期国债在各交易场所以现券买卖和回购的方式上市交易。 四、本期国债低于票面面值贴现发行，2011年7月18日(节假日顺延)按面值偿还。 五、本期国债在2011年4月18日至4月20日的发行期内，采取场内挂牌和场外签订分销合同的方式分销，分销对象为在中国证券登记结算有限责任公司开立股票和基金账户，在中央国债登记结算有限责任公司开立债券账户的各类投资者。通过各交易场所分销部分，由承销机构根据市场情况自定价格。 特此公告。 中华人民共和国财政部 二O一一年四月十五日 中华人民共和国财政部公告2011年第19号 根据国家国债发行的有关规定，财政部决定续发行2011年记账式附息(一期)国债(以下简称本期国债)，现将有关事项公告如下： 一、本期国债通过全国银行间债券市场（含试点商业银行柜台）、证券交易所债券市场(以下简称各交易场所)面向社会各类投资者续发行。试点商业银行包括中国工商银行股份有限公司、中国农业银行股份有限公司、中国银行股份有限公司、中国建设银行股份有限公司、招商银行股份有限公司、中国民生银行股份有限公司、北京银行股份有限公司和南京银行股份有限公司在全国已经开通国债柜台交易系统的分支机构(以下简称试点银行)。
国家税务总局 关于发布《营业税改征增值税试点地区适用增值税零税率应税服务免抵退税管理办法（暂行）》的公告 国家税务总局公告2012年第13号 字体：【大】【中】【小】 为确保营业税改征增值税试点工作顺利实施，根据《财政部国家税务总局关于应税服务适用增值税零税率和免税政策的通知》（财税〔2011〕131号）等相关规定，经商财政部，国家税务总局制定了《营业税改征增值税试点地区适用增值税零税率应税服务免抵退税管理办法（暂行）》。现予以发布，自2012年1月1日起施行。 零税率应税服务提供者目前暂按出口货物退（免）税申报系统中出口货物免抵退税申报表格式报送申报表和电子申报数据，申报表填表口径和方法由上海市国税局另行明确。本办法附件1、附件2、附件3启用时间另行通知。 与本办法相关的财政负担机制、免抵税款调库方式另行明确。 特此公告。 附件：1.零税率应税服务（国际运输）免抵退税申报明细表 2.应税服务（研发、设计服务）免抵退税申报明细表 3.向境外单位提供研发、设计服务收讫营业款明细清单 国家税务总局 二○一二年四月五日
附件1 零税率应税服务（国际运输）免抵退税申报明细表 海关企业代码： 企业名称： (公章) 填表说明： 1.对前期申报错误的，本期可进行调整。前期少报应税服务营业额或低报征、退税率的，可在本期补报；前期多报应税服务营业额或高报征、退税率的，本期可以负数(或红字)数据冲减；也可用负数(或红字)将前期错误数据全额冲减，再重新申报正数数据。 2.“序号”栏由4位流水号构成(如0001、0002、…，序号要与申报退税的资料装订顺序保持一致； 3.第1栏“应税服务代码” 及第2栏“应税服务名称”按出口退税率文库中的对应编码和服务名称填写； 4.第3栏“本期运输次数”填写在该应税服务代码下，本所属期发生的国际运输次数； 5.第4栏“自运舱单份数”填写在该应税服务代码下，本所属期发生的国际运输所对应的自运舱单份数； 6.第5栏“自运提单（运单）份数或载客人数”为载货运输的填写在该应税服务代码下，本所属期所发生的国际运输所对应的自运提单或运单份数，载客运输的填写在该应税服务代码下，本所属期发生的国际运输所对应的载客人数； 7.第6栏“应税服务营业额(折人民币)”为提供应税服务取得的全部价款（包括尚未收取但以获得收取权利）的人民币金额，以其他币种结算的填写折算人民币金额； 8.第7栏“支付给非试点纳税人价款”为服务出口企业支付给未进行营业税改征增值税的营业税纳税人的费用； 9.第8栏“免抵退税计税金额”为应税服务营业额扣除支付给非试点纳税人价款后的余额，即第6栏减第7栏； 10.第9栏“征税率”为在境内提供应税服务法定增值税税率； 11.第10栏“退税率”为应税服务在代码库中对应的增值税退税率； 12.第11栏“应税服务免抵退税计税金额乘征退税率之差”按第8栏×(第9栏-第10栏)计算填报； 13.第12栏“应税服务免抵退税计税金额乘退税率”按第8栏×第10栏计算填报；
国家税务总局关于纳税人资产重组有关增值税问题的公告 2011年第13号 根据《中华人民共和国增值税暂行条例》及其实施细则的有关规定，现将纳税人资产重组有关增值税问题公告如下： 纳税人在资产重组过程中，通过合并、分立、出售、置换等方式，将全部或者部分实物资产以及与其相关联的债权、负债和劳动力一并转让给其他单位和个人，不属于增值税的征税范围，其中涉及的货物转让，不征收增值税。 本公告自2011年3月1日起执行。此前未作处理的，按照本公告的规定执行。《国家税务总局关于转让企业全部产权不征收增值税问题的批复》（国税函〔2002〕420号）、《国家税务总局关于纳税人资产重组有关增值税政策问题的批复》（国税函〔2009〕585号）、《国家税务总局关于中国直播卫星有限公司转让全部产权有关增值税问题的通知》（国税函〔2010〕350号）同时废止。 特此公告。 二○一一年二月十八日 分送：各省、自治区、直辖市和计划单列市国家税务局、地方税务局。 解读总局《关于纳税人资产重组有关增 值税问题的公告》 日前，国家税务总局下发了《关于纳税人资产重组有关增值税问题的公告》（国家税务总局公告2011年第13号），就纳税人资产重组有关增值税问题公告如下：纳税人在资产重组过程中，
通过合并、分立、出售、置换等方式，将全部或者部分实物资产以及与其相关联的债权、负债和劳动力一并转让给其他单位和个人，不属于增值税的征税范围，其中涉及的货物转让，不征收增值税。 第13号公告虽然言简意赅，但是意义重大。反映了国家对资产重组税收政策的支持。笔者认为，可以从以下几个方面对本公告进行理解和把握。 1．关于资产重组 在理解13号公告相关内容前，我们可以先了解一下资产重组的相关常识。 资产重组是指企业资产的拥有者、控制者与企业外部的经济主体进行的，对企业资产的分布状态进行重新组合、调整、配置的过程，或对设在企业资产上的权利进行重新配置的过程。包括企业合并和分立、资产剥离或所拥有股权出售、资产置换等公司资产(含股权、债权等)与公司外部资产或股权互换的活动。 2．纳税人在资产重组过程中，合并、分立、出售、置换所涉及的货物转让，不征收增值税 本条是13号公告的核心和关键。此前，虽然学界也是认为合并或分立等方式涉及的货物转让不需要缴纳增值税，但是毕竟
四川省国家税务局公告 2011年第5号 四川省国家税务局 关于单用途商业预付卡有关增值税问题的公告 现将单用途商业预付卡有关增值税问题公告如下： 单用途商业预付卡（含储值卡、购物卡、提货卡等，以下简称“单用途预付卡”）是由纳税人发行，只在本单位或同一品牌连锁商业企业或加盟企业购买商品、服务的一类预付卡。对纳税人销售单用途预付卡的增值税问题，应根据纳税人业务的不同情况，按以下方式分别处理： 一、纳税人销售单用途预付卡，售卡收款时未开具发票的，可在交易实际发生时按交易金额结转主营业务收入并计提销项税额。 二、纳税人发行单用途预付卡，售卡收款时即开具发票的，其增值税纳税义务发生时间为开具发票的当天。纳税人可采取财务与税务会计处理分离的方式进行账务处理： （一）开具发票时，按17%的税率计提销项税额： 借：银行存款（现金、应收账款） 贷：预收账款 应交税金——应交增值税（销项税额） （二）月末按规定确认当期主营业务收入后，按确认收入进行账务处理，同时结转成本： 借：预收账款 贷：主营业务收入 借：主营业务成本 贷：库存商品 （三）销售货物既有适用17%税率的，也有13%税率的，月末按规定确认当期主营业务收入后，将适用13%税率的部分多计提的销项税额用红字冲减，相应调整对应科目： 借：主营业务收入（红字）
贷：应交税金——应交增值税（销项税额）（红字） （四）销售货物既有征税货物，也有免税货物的，月末按规定确认当期主营业务收入后，将免税货物已计提的销项税额用红字冲减，相应调整对应科目。 借：主营业务收入（红字） 贷：应交税金——应交增值税（销项税额）（红字） （五）预付卡既用于购买货物又用于消费非应税项目（如商场中的咖啡厅、餐厅、电影院）的，月末按规定确认当期主营业务收入后，将已计提的销项税额用红字冲减，相应调整对应科目： 借：主营业务收入（红字） 贷：应交税金——应交增值税（销项税额）（红字） 三、对在我省范围内使用单用途预付卡跨店消费，售卡门店与实际消费门店不一致的，按以下方式处理： （一）实际消费门店月末按规定确认当期主营业务收入后，按适用税率计提销项税额。 借：银行存款（应收账款） 贷：主营业务收入 应交税金——应交增值税（销项税额） （二）销售单用途预付卡的门店，对在我省范围内其他门店进行消费的部分，月末按内部结算单将已计提的销项税额用红字冲减，相应调整对应科目。 借：预收账款（或其他往来科目） 贷：银行存款（或其他往来科目） 应交税金——应交增值税（销项税额）（红字） 四、根据《国家税务总局关于修订<增值税发票使用规定>的通知》（国税发［2006］156号）文件的规定，由于纳税人销售单用途预付卡时不能确定实际交易货物项目，因此不得开具增值税专用发票。 本公告自2011年10月1日施行。 二○一一年八月三十一日
《关于纳税人资产重组增值税问题的公告》解读 作者不详，文件摘自网络 国家税务总局2011年第13号公告彻底颠覆了国税函【2002】420号文件和国税函【2009】585号文件的规定，反映了国家对资产重组税收政策的支持，意味着日前国务院多次强调的对重组业务给予政策支持，变为了现实。新年伊始资产重组增值税政策非常给力！ 该文件如是表述：纳税人在资产重组过程中，通过合并、分立、出售、置换等方式，将全部或者部分实物资产以及与其相关联的债权、负债和劳动力一并转让给其他单位和个人，不属于增值税的征税范围，其中涉及的货物转让，不征收增值税。 本公告自2011年3月1日起执行。此前未作处理的，按照本公告的规定执行。《国家税务总局关于转让企业全部产权不征收增值税问题的批复》（国税函〔2002〕420号）、《国家税务总局关于纳税人资产重组有关增值税政策问题的批复》（国税函〔2009〕585号）、《国家税务总局关于中国直播卫星有限公司转让全部产权有关增值税问题的通知》（国税函〔2010〕350号）同时废止。 文件虽言简意赅，但是意义重大，笔者初读有七个认识： 第一，明确合并、分立中涉及的货物不缴纳增值税，终于说了个痛快话！此前虽然一般认为，合并分立是不需要缴纳增值税的，但是毕竟没有正式文件，在执行过程中，总是套用国税函【2002】420号文件，还要加上若干解释工作来前顾后盼，纳税人心里没底儿。有的税务局认为合并不征税，分立要征税。笔者日前见到的一个案例，某省级税务机关就是坚持这个观点的。总局这么多年，一直就是不说句明白话，这下子，多年之隐，一时了之！ 第二，在重组中的出售和置换方式，也纳入不征收增值税范围，认为也属于产权交易。虽然出售、置换只有短短的四个字，真的是意义重大，意味着大连金牛们得到了彻底的解放，大连金牛将其全部资产以及与其关联的债权、债务、劳
国家税务总局公告2011年第25号 关于发布《企业资产损失所得税税前扣除管理办法》的公告 现将《企业资产损失所得税税前扣除管理办法》予以发布，自2011年1月1日起施行。 特此公告。二○一一年三月三十一日【国家税务总局】【2011】【企业所得税】【资产损失】 企业资产损失所得税税前扣除管理办法 第一章总则 第一条根据《中华人民共和国企业所得税法》（以下简称企业所得税法）及其实施条例、《中华人民共和国税收征收管理法》（以下简称征管法）及其实施细则、《财政部、国家税务总局关于企业资产损失税前扣除政策的通知》（财税[2009]57号）（以下简称《通知》）的规定，制定本办法。 第二条本办法所称资产是指企业拥有或者控制的、用于经营管理活动相关的资产，包括现金、银行存款、应收及预付款项（包括应收票据、各类垫款、企业之间往来款项）等货币性资产，存货、固定资产、无形资产、在建工程、生产性生物资产等非货币性资产，以及债权性投资和股权（权益）性投资。 第三条准予在企业所得税税前扣除的资产损失，是指企业在实际处置、转让上述资产过程中发生的合理损失（以下简称实际资产损失），以及企业虽未实际处置、转让上述资产，但符合《通知》和本办法规定条件计算确认的损失（以下简称法定资产损失）。 第四条企业实际资产损失，应当在其实际发生且会计上已作损失处理的年度申报扣除；法定资产损失，应当在企业向主管税务机关提供证据资料证明该项资产已符合法定资产损失确认条件，且会计上已作损失处理的年度申报扣除。 第五条企业发生的资产损失，应按规定的程序和要求向主管税务机关申报后方能在税前扣除。未经申报的损失，不得在税前扣除。 第六条企业以前年度发生的资产损失未能在当年税前扣除的，可以按照本办法的规定，向税务机关说明并进行专项申报扣除。其中，属于实际资产损失，准予追补至该项损失发生年度扣除，其追补确认期限一般不得超过五年，但因计划经济体制转轨过程中遗留的资产损失、企业重组上市过程中因权属不清出现争议而未能及时扣除的资产损失、因承担国家政策性任务而形成的资产损失以及政策定性不明确而形成资产损失等特殊原因形成的资产损失，其追补确认期限经国家税务总局批准后可适当延长。属于法定资产损失，应在申报年度扣除。 企业因以前年度实际资产损失未在税前扣除而多缴的企业所得税税款，可在追补确认年度企业所得税应纳税款中予以抵扣，不足抵扣的，向以后年度递延抵扣。 企业实际资产损失发生年度扣除追补确认的损失后出现亏损的，应先调整资产损失发生年度的亏损额，再按弥补亏损的原则计算以后年度多缴的企业所得税税款，并按前款办法进行税务处理。 第二章申报管理 第七条企业在进行企业所得税年度汇算清缴申报时，可将资产损失申报材料和纳税资料作为企业所得税年度纳税申报表的附件一并向税务机关报送。 第八条企业资产损失按其申报内容和要求的不同，分为清单申报和专项申报两种申报形式。其中，属于清单申报的资产损失，企业可按会计核算科目进行归类、汇