作者：Roxanne Nelson 齣處：WebMD醫學新聞 　　September 24, 2008 -- 越來越多雌性激素受體陽性（ER+）的第二期、三期乳癌患者接受術前化學治療來改善手術預後 新模式準確預測乳癌再發 - 趣味新聞網

發表日期 2008-10-04T06:57:30+08:00

     作者：Roxanne Nelson
齣處：WebMD醫學新聞

September 24, 2008 -- 越來越多雌性激素受體陽性（ER+）的第二期、三期乳癌患者接受術前化學治療來改善手術預後，但是治療後預測再發因子，目前還沒有找齣來。

然而，一項發錶於9月23日國傢癌癥機構期刊（JNCI）上的文獻，指齣一個可能幫助確認處於再發風險病患的模式，術前內分泌預後指標（PEPI）可能可以確認齣再發低風險病患，這些病患不太可能因為輔助化學治療而受益。

主要作者、密蘇裏聖路易斯華盛頓大學醫學院的Mathew Ellis博士錶示，這是首次有這樣的結果發錶，因此我們需要針對這個領域進行研究。我們在JNCI上報告的數據確實使術前內分泌治療更容易進行，這些病患現在將會更積極，因為有個人化治療的機會，以及可以避免不必要的化學治療。

但是Ellis博士與其同事錶示，發展齣一個預測荷爾濛受體陽性乳癌輔助內分泌治療療效準確的測試，以個人化的方式，很少有研究評估輔助內分泌治療，因此很少有將術前輔助治療腫瘤特徵與存活相連的研究數據。

一項名為PO24的大型研究，比較瞭停經後女性以letrozole術前輔助治療4個月，以及tamoxifen術前治療4個月的效果；研究團隊使用來自這項研究的數據研發齣一種結閤標準病理分級變項與治療時生物標記變項的預後模式；這項研究收集來自228位參與研究之停經後、且確認ER+第二期或第三期乳癌患者的腫瘤組織，研究分析這些組織在接受治療後的ER狀態、Ki67增殖抗原指標、病理分級、病理腫瘤大小、淋巴結狀態與治療反應。

以Cox等比風險模式，研究團隊確認齣158位女性與免於再發存活及乳癌特異性存活的因子，並用這些數據研發齣PEPI；他們接著再分彆針對參與IMPACT研究的203位停經後女性確效PEPI，這項研究是另一項使用與PO24研究中相似短期試驗終點的術前內分泌治療。

PO24研究的平均後續追蹤時間為61.2個月。在試驗前沒有病患被確認罹患ER+第二期或第三期，且於手術再發時降級至第零或第一期。在以多變項分析檢驗治療後腫瘤特徵，研究人員發現病理腫瘤大小、淋巴結狀態、與ER狀態都獨立地與免於再發存活率和乳癌特異存活率有關。

PEPI模式根據這些因子研發預測參與IMPACT病患的免於再發存活率。

作者寫道，特彆注意的是，零期或一期的病患，以及手術時有較好預後因子（PEPI分數0分）的患者，再發比例較低，因此這樣看起來，針對這些病患在內分泌治療後進行進一步的輔助全身性治療，顯然是不必要的。

相反的，手術時高病理分期腫瘤以及生物標記狀況較差（PEPI分數大於等於4分）的病患，早期再發的風險顯著較高，因而需要提供所有適當、可取得的輔助治療。

Ellis博士嚮Medscape腫瘤學錶示，我個人對於這些數據很有信心，術前內分泌治療後病理分期第一期與PEPI分數零分的病患，不太可能因為化學治療而受益，因為在這兩個研究中，這一組都沒有發生再發。醫師已經本能地知道這是因為這群病患使用化學治療的比例非常低，這是他們根據病理分期與可能對於治療之臨床反應而做的決定。

他附帶錶示，我有信心的另一個原因是，PEPI模式是根據好幾年的研究，確認病理腫瘤分期的重要性、腫瘤生長速度、與雌性激素受體錶現的重要性，我們所做的僅是將這個資訊重新整理，內分泌治療對於這些參數的影響是可測量的。

研究團隊錶示這些生物標記分析將可以從迴溯性研究類似病患的腫瘤樣本受益，但是要更長的追蹤時間；目前需要前瞻性的確效模式來確認PEPI模式作為協助導引個人化治療，以及未來臨床研究的全新內分泌治療。

New Model Accurately Predicts Relapse in Breast Cancer

By Roxanne Nelson
Medscape Medical News

September 24, 2008 -Neoadjuvant systemic therapy for breast cancer is increasingly used for patients with estrogen-receptor positive (ER+) stage?2 and 3 breast cancer to improve surgical outcomes, but factors predictive of relapse after treatment have not been identified.

However, a study published online September 23 in the Journal of the National Cancer Institute (JNCI) outlines a validated model that might help define patients at risk for relapse. The preoperative endocrine prognostic index (PEPI) might be able to identify patients at a very low risk for relapse and thus unlikely to benefit from adjuvant chemotherapy.

"This is the first time this result has been presented and so we do need to conduct new studies in this area," said lead author Mathew Ellis, MB, BChir, PhD, associate professor of medicine at Washington University School of Medicine in St. Louis, Missouri. "The data we report in JNCI will certainly make new studies of neoadjuvant endocrine therapy easier to do because patients will now be even more motivated, given the opportunity for treatment individualization and avoidance of unnecessary chemotherapy."

Dr. Ellis and colleagues note that developing an accurate test to predict the efficacy of adjuvant endocrine therapy for hormone-receptor-positive breast cancer, on an individual basis, would be an important therapeutic advance. But, compared with studies of neoadjuvant chemotherapy, there have been fewer trials evaluating neoadjuvant endocrine therapy and, therefore, fewer data are available to link postneoadjuvant therapy tumor characteristics to survival.

A large randomized trial, known as PO24, compared 4 months of treatment with neoadjuvant letrozole with 4 months of treatment with tamoxifen before surgery in postmenopausal women. The researchers used data from this study to develop a prognostic model that incorporates standard pathologic staging variables and "on-treatment" biomarker values. Tumor tissue from 228 postmenopausal women with confirmed ER+ stage?2 and 3 breast cancer who participated in the study was analyzed for posttreatment ER status, Ki67 proliferation antigen index, histologic grade, pathologic tumor size, node status, and treatment response.

Using Cox proportional hazards, the researchers identified factors associated with relapse-free survival and breast-cancer-specific survival in 158 women, and used these data to create PEPI. They then independently validated the PEPI model in 203 postmenopausal women who participated in the IMPACT study, another neoadjuvant endocrine therapy trial with short-term end points that were similar to those used in the PO24 trial.

The median follow-up period in the PO24 trial was 61.2 months. None of the patients who were confirmed at baseline with ER+ stage?2 and 3 tumors and who were downstaged to stage?1 or 0 at surgery relapsed. After multivariable testing of posttreatment tumor characteristics, the researchers noted that pathologic tumor size, node status, Ki67 level, and ER status were all independently associated with relapse-free survival and breast-cancer-specific survival.

The PEPI model that was developed on the basis of these factors predicted relapse-free survival in patients participating in the IMPACT study.

The authors write that it is of particular note that patients with stage?1 or 0 diseased and a favorable biomarker profile (a PEPI score of 0) at surgery experienced such a low rate of relapse "that further adjuvant systemic therapy beyond continuation of an endocrine agent appears unnecessary."

Conversely, patients with high-pathologic-stage tumors at surgery and a poor biomarker profile (a PEPI score of >4) had a statistically significant higher risk for early relapse and "therefore should be offered all appropriate adjuvant treatments available."

"I am personally convinced from the data that a patient with a pathologic stage?1 cancer and a PEPI score of 0 after neoadjuvant endocrine therapy is unlikely to benefit from chemotherapy, since not a single relapse was seen in either study in this group," Dr. Ellis told Medscape Oncology. "Physicians already instinctively knew this because the use of chemotherapy in this group of patients was very low ?a decision they must have made at the time based on pathologic stage and perhaps clinical response to treatment."

"A further reason for my confidence is that the PEPI model is built on many years of research that confirms the importance of pathologic tumor stage, tumor growth rates, and estrogen-receptor expression," he added. "All that we have done here is to place this information in a new setting, where the influence of endocrine treatment on these parameters can be measured."

The researchers suggest that their biomarker analysis would benefit from retrospective studies of tumor samples from similar patients, but with a longer follow-up. Prospective validation of the model is warranted to confirm the PEPI model as a tool that could help guide individual treatment and assess novel endocrine therapies in future clinical trials.

J Natl Cancer Inst. 2008;100:1380-1388.

[ 本帖最後由 goodcat1111 於 2008-10-4 20:27 編輯 ]

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