Dr.
Terry Mamounas, MD
Aultman Cancer Center
Canton, Ohio, USA
对于这个II期可手术的患者来说，辅助化疗和新辅助化疗同样可以延长其无病生存和总生存。1而应用新辅助化疗可能具有什么优势呢？新辅助化疗可产生80％左右的临床缓解率和10-15％的病理性完全缓解。2由于肿瘤缩小，更多的患者可以接受保乳手术。从这个意义上讲，如果患者由于肿瘤和乳房大小比例问题而不能行保乳手术的话，我倾向于选择新辅助化疗。另一方面，如果患者初诊时适合做乳房肿瘤切除术，那么辅助化疗或新辅助化疗都是合理的选择。新辅助化疗的另一潜在优势在于可以通过肿瘤的缓解来预测患者的长期生存。1
In this patient with clinical stage II operable breast
cancer, adjuvant and neoadjuvant chemotherapy are equally
effective in prolonging disease-free and overall survival.1
What might be some advantages for using the neoadjuvant
approach? Neoadjuvant chemotherapy induces clinical response
in about 80% of the cases and pathologic complete response
in about 10-15%.2 As a result of tumor shrinkage, more
patients are able to undergo lumpectomy. From that standpoint,
if the patient were not a candidate for lumpectomy based
on tumor size/breast size ratio, I would favor the neoadjuvant
approach. If, on the other hand, the patient is a good
lumpectomy candidate at the time of diagnosis, either
approach (adjuvant or neoadjuvant) is reasonable. One
other potential advantage of the neoadjuvant approach
is the opportunity to correlate tumor response with long
term outcome.1 随着新方案临床研究结果的产生和老方案的成熟，化疗方案（无论是辅助还是新辅助化疗）的应用目前正成为争论的焦点。目前回顾性分析证实蒽环类方案较非蒽环类方案产生了微小但具有统计学意义的生存优势3，因此我倾向于应用含蒽环类方案。而越来越多的证据表明含蒽环类和5-FU的方案6周期治疗(如CAF和CEF)可能优于4个周期的AC；但是目前尚无直接对照研究证实此结果，一线协作组正在计划这类试验。因此，尽管还缺乏确定的数据，但如果该患者计划接受单纯的含蒽环类方案治疗，那么选用6周期的CAF或CEF方案而非4周期的AC是合理的。
The regimen of chemotherapy to be used (either as adjuvant
or neoadjuvant) is currently a subject of controversy,
and one that is evolving as new adjuvant studies produce
results and older ones mature. I would favor an anthracycline-containing
regimen based on the results from the overview analysis
demonstrating a small but statistically significant
advantage in overall survival with anthracycline-containing
regimens verses non-anthracycline-containing ones.3
There is increasing evidence, however, that anthracycline
containing regimens administered for 6 cycles and containing
5-FU (such as CAF or CEF) might be superior to 4 cycles
of AC; however, a direct comparison has not been made
and is currently being planned by the cooperative groups.
So if this patient was to be treated with an anthracycline-containing
regimen alone, there might be some rationale for using
CAF or CEF for 6 cycles rather than 4 cycles of AC,
although definitive data are lacking.
紫杉类药物在化疗方案中的角色和紫杉类药物与其他化疗药物联合应用的最佳方法仍然是争论的主题。到目前为止，两项大型在淋巴结阳性患者中所进行的辅助临床研究（CALBG
9344 和 NSABP B-28）以及一项在可手术患者中的大规模新辅助临床研究（NSABP B-27）已经得到了应用AC序贯紫杉醇或多西紫杉醇（泰索帝）的结果。第一项辅助研究的最终结果显示出与单纯应用AC相比，加入紫杉醇序贯治疗产生了微小但有统计学意义的无病生存和总生存的改善（复发危险性降低了17％，死亡危险性下降18％）。4
并且激素受体阴性的患者接受紫杉醇序贯治疗受益最多（复发和死亡危险性分别降低了25％和22％），尽管这是未计划的亚组分析结果。
第二项辅助治疗研究的分析（中位随访65月）显示出与单纯AC相比，加入紫杉醇序贯治疗使得疾病复发危险性下降了17％(p=0.008)，但没有降低疾病死亡的危险性。5然而，与CALGB9344的研究结果相反，NSABP
B-28研究显示出在激素受体阳性患者中加入紫杉醇序贯治疗降低了疾病复发的危险性(-21%，p=0.30)，说明在紫杉醇辅助治疗中激素受体状态仍然是一个重要的考虑因素。NSABP
B-27研究比较了单独应用AC新辅助或AC新辅助后加入泰索帝序贯治疗或术后泰索帝辅助治疗的疗效。结果显示，与单纯术前AC化疗相比，加入泰索帝序贯治疗可明显提高临床完全缓解率（从40％到65％）和病理完全缓解率
(从 13.7% 到 25.6%) 以及腋窝淋巴结阴性的患者比例 (51.5% vs. 59.5%),6
提示了AC后序贯应用泰索帝可提高抗肿瘤活性。但这项研究的最后生存结果尚未公布。
The role of taxanes in the chemotherapy regimen and
the optimal way of integrating them with the other chemotherapy
agents is also an evolving matter of debate. So far,
two large adjuvant trials in node-positive patients
(CALBG 9344 and NSABP B-28) and one large neoadjuvant
trial (NSABP B-27) in patients with operable breast
cancer have produced results using the sequential administration
of paclitaxel or docetaxel following AC. Mature results
from the first adjuvant trial show a small but statistically
significant improvement in disease-free survival (17%
reduction in the odds of recurrence) and in overall
survival (18% reduction in the odds of death) with the
addition of paclitaxel to AC.4
Most of the benefit was seen in receptor negative patients
(25% reduction in the odds of recurrence and 22% reduction
in the odds of death), although this subset analysis
was unplanned.
Final results from the second trial (with 65 months
of median follow up) demonstrated that the addition
of Paclitaxel significantly reduced the risk of recurrence
by 17%, but there was no significant difference in the
risk of death.5 In contrast to CALGB 9344, NSABP B-28
suggested a 21% reduction in the risk of recurrence
in HR-positive breast cancer.Because of this, it appears
as if HR status will remain an important consideration
in Paclitaxel therapy. The NSABP B-27 trial compared
neoadjuvant or adjuvant docetaxel following neoadjuvant
AC to neoadjuvant AC alone. The addition of neoadjuvant
docetaxel significantly increased clinical complete
response rates (from 40% to 65%), pathologic complete
response rates (from 13.7% to 25.6%) and the percentage
of patients with histologically negative axillary nodes
(51.5% verses 59.5%)6, indicating additional antitumor
activity with sequential docetaxel following AC. However,
outcome results from this trial are not available yet.
II、III期临床均证实紫杉类联合蒽环类治疗晚期乳腺癌具有较高的疗效，由此许多辅助临床试验比较了或正在比较紫杉类联合蒽环类(加或不加环磷酰胺)与AC、FAC或AC序贯紫杉类的疗效。这些研究的结果将最终确立紫杉类药物在在乳腺癌辅助治疗中的地位。
Combinations of anthracyclines and taxanes have been
found to be very active in phase II-III trials in patients
with advanced breast cancer and several adjuvant trials
have compared or are in the process of comparing anthracycline-taxane
combinations (with or without cyclophosphamide) to AC,
FAC or AC followed by taxane. The results of these trials
will demonstrate the rule of Taxanes in the adjuvant
therapy of breast cancer.
总之，这个患者可以进行辅助或新辅助化疗。为了有利于保乳手术的进行，我倾向于应用新辅助化疗。关于化疗方案的选择，不论她是淋巴结阳性或高危淋巴结阴性患者，我建议采用AC序贯紫杉类方案。尽管紫杉醇在淋巴结阳性患者中显示出了活性，即使这个患者是淋巴结阴性，但鉴于肿瘤大小和受体状态，我们在这个患者中同样可以考虑应用紫杉醇。相似的，尽管目前泰索帝在新辅助化疗上尚无成熟的研究结果，我们仍然可以推断出在NSABP
B-27中病理性完全缓解率的提高可能最终会转换成无病生存和总生存的改善，但这仍需要被证实。如果这个患者要接受非紫杉类的治疗，我倾向于应用6个周期的CAF或CEF方案。
In summary, this patient can be treated with adjuvant
or neoadjuvant chemotherapy. I would favor neoadjuvant
therapy in order to facilitate the performance of lumpectomy,
if she is not otherwise a candidate for it. Regarding
the chemotherapy regimen to be used, given that she
is either node-positive or high-risk node negative,
I would favor the sequential regimen of AC followed
by a taxane. Although paclitaxel has shown activity
in the node-positive setting, one can consider it even
if this patient is node-negative, given the tumor size
and receptor status. Similarly, although there are presently
no mature outcome results with docetaxel in the adjuvant
or neoadjuvant setting, one could extrapolate that the
observed increase in pathologic response rates seen
in NSABP B-27 might eventually translate to improvement
in disease-free and/or overall survival but that remains
to be proven. If the patient were to be treated without
taxanes, I would favor 6 cycles of CAF or CEF.
参考文献
References
1. Fisher B. Bryant J, Wolmark N, et al: Effect of Preoperative
Chemotherapy on the Outcome of Women with Operable Breast
Cancer. J Clin Oncol; 16:2672-2685, 1998.
2. Fisher B, Brown A, Mamounas E, et al: The Effect
of Preoperative Chemotherapy on Local-Regional disease
in Women with Operable Breast Cancer: Findings from
NSABP B-18. J Clin Oncol; 15:2483-93,1997.
3. Polychemotherapy for early breast cancer: an overview
of the randomised trials. Early Breast cancer Trialists'
Collaborative Group. Lancet 1998; 352:930-42.
4. Henderson IC: NIH Consensus Development Conference,
November 1-3, 2000, Bethesda, MD.
5. Mamounas EP: NIH Consensus Development Conference,
November 1-3, 2000, Bethesda, MD.
6. Bear H: The effect on primary tumor response of adding
sequential Taxotere to Adriamycin and cyclophosphamide:
preliminary results from NSABP protocol B-27. Breast
Cancer Res Treat 2001; 69:210, Abstract 5.
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