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作者：Breast Cancer,aspirin,metastasis  
出處：WebMD醫學新聞

　　February 17, 2010 — 根據線上發表於2月16日臨床腫瘤學期刊(Journal of Clinical Oncology)的資料，規律使用阿斯匹靈或許可以增加乳癌病患的存活，使用阿斯匹靈與降低遠端復
　　
　　發、乳癌死亡、任何原因死亡等風險有關。
　　
　　根據每週使用阿斯匹靈的天數，病患可以降低遠端轉移風險達43%至60%，同樣地，相較於未使用者，使用阿斯匹靈與乳癌相關死亡率降低64%至71%有關。
　　
　　第一作者、麻州波士頓哈佛醫學院醫學助理教授Michelle?D. Holmes博士表示，重點在於瞭解，這是一個觀察型研究，在這類型的研究中，我們無法證實阿斯匹靈造成存活改善，
　　
　　看看其他觀察型研究結果是否和我們的一樣，將是未來的重點。
　　
　　Holmes博士向Medscape Oncology表示，進行研究確認阿斯匹靈如何改善存活也很重要。
　　
　　她也強調，研究中的所有婦女都接受了傳統的乳癌治療，包括手術、放射線治療、化療、荷爾蒙治療。她們服用的阿斯匹靈並未取代這些治療，它是加入這些治療，另外，也須瞭
　　
　　解，服用阿斯匹靈可能會有一些不好的副作用，如胃腸道出血。
　　
　　Holmes博士指出，需要臨床試驗才能證實阿斯匹靈可以改善乳癌婦女的存活，以及改變臨床實務，不過，已經因為其他原因而接受醫師建議服用阿斯匹靈的婦女，應對於阿斯匹
　　
　　靈可能可以預防她們的乳癌復發感到欣慰。
　　
　　【之前的研究沒有結論】
　　作者們寫道，實驗型研究顯示，阿斯匹靈可以抑制乳癌細胞的生長和減少侵犯性，減少骨轉移中的細胞激素，刺激免疫反應。此外，阿斯匹靈或其他非類固醇抗發炎藥物的統合分
　　
　　析顯示，使用它們與乳癌發生率風險降低9%至30%有關，不過，作者們指出，使用阿斯匹靈和乳癌發生率之間的關聯依舊沒有結論。
　　
　　在目前的研究中，作者們假設，乳癌診斷之後使用阿斯匹靈與乳癌相關死亡風險降低和第1-3期疾病之遠端復發風險降低有關。
　　
　　他們進行了一個前瞻性觀察研究，包括了「Nurses' Health Study (NHS)」研究於1976-2002年間的4165名女性研究對象，她們的診斷為第1、2、3期乳癌。這些婦女被觀察直到
　　
　　2006年或者死亡為止，看哪種先發生。
　　
　　在這個世代中，有341例乳癌相關死亡，400例遠端復發(包括前述的341例乳癌死亡)，以及732名死於其他原因。診斷後未提供阿斯匹靈評估情況的乳癌婦女有2910人。
　　
　　初級結果是根據每週使用阿斯匹靈天數(0、1、2- 5、6或 7天)的乳癌死亡風險，在診斷之後至少12個月時評估，之後照著更新。
　　
　　Holmes博士表示，我們在她們的乳癌診斷之後測量她們的阿斯匹靈服用情況，儘可能不要在她們診斷之後的第一年評估她們的阿斯匹靈服用情形，因為那時候她們可能正在接受
　　
　　放射線治療和化療，且當時可能不建議服用阿斯匹靈。
　　
　　他們的結果顯示，使用阿斯匹靈與乳癌死亡風險降低有關，結果並未因疾病分期、身體質量指數、停經狀態、雌激素受體狀態等而有顯著不同，這些結果全部都是更值得注意的，
　　
　　因為NHS未能發現使用阿斯匹靈和乳癌發生率之間的關聯。
　　
　　相較於未曾使用者，乳癌死亡率的累積校正相對風險(RRs)是：
　　* 過去使用者為0.88 (95%信心區間[CI]，0.64- 1.22)
　　* 目前每週使用1天者為1.07 (95% CI，0.70- 1.63)
　　* 目前每週使用2-5天者為0.29 (95% CI，0.16- 0.52)
　　* 目前每週使用6或7天者為0.36 (95% CI，0.24- 0.54)。
　　
　　遠端復發的結果相似；使用阿斯匹靈天數1、2- 5、6或 7天者之校正RR為分別0.91 (95% CI，0.62- 1.33)、0.40 (95% CI，0.24- 0.65)、0.57 (95% CI，0.39- 0.82)。
　　
　　此外，使用阿斯匹靈與任何原因之死亡率風險降低有關；過去使用阿斯匹靈、目前每週使用1天、目前每週使用2-5天、目前每週使用6或7天者的整體死亡率累積RR分別是0.96
　　
　　(95% CI，0.76- 1.21) 、0.94 (95% CI，0.67- 1.32)、0.53 (95% CI，0.37- 0.76)、0.54 (95% CI，0.41- 0.70)。
　　
　　至於所有原因的死亡率，作者們指出，與阿斯匹靈有關的保護效果顯然是因為受到對乳癌死亡率的影響。
　　
　　他們推測，乳癌死亡和使用阿斯匹靈之間的關聯比復發更強烈，因為復發比死亡更可能被錯誤分類，使用阿斯匹靈的期間也有適度的關聯，作者們也指出，使用阿斯匹靈會影響癌
　　
　　症路徑中的近端事件而非遠端事件。
　　
　　他們結論表示，若經確認，我們的結果將擴大現有的降低乳癌相關發病率與死亡率之介入方式的機會。
　　
　　國家健康研究中心資助本研究，作者們皆宣告沒有相關財務關係。
　　
　　J Clin Oncol. 線上發表於2010年2月16日。


Aspirin May Boost Survival in Breast Cancer

By Breast Cancer,aspirin,metastasis
Medscape Medical News

February 17, 2010 — The regular use of aspirin might increase survival in breast cancer, according to data published online February?16 in the Journal of Clinical Oncology. Aspirin use was associated with a decreased risk for distant recurrence, breast cancer death, and death from any cause.

Depending on the number of days of aspirin use per week, patients were able to reduce the risk for distant metastasis by 43% to 60%. Likewise, compared with nonusers, aspirin use was associated with a 64% to 71% reduction in the risk for breast cancer-related mortality.

"It is important to realize that this is an observational study, and in such a study we cannot prove that aspirin causes improved survival," said lead author Michelle?D. Holmes, MD, DrPH, assistant professor of medicine at Harvard Medical School in Boston, Massachusetts. "It will be important to see if our results can be repeated in other observational studies."

It will also be important, Dr. Holmes told Medscape Oncology, to undertake studies to determine how aspirin might improve survival.

The aspirin they took was not a substitute for these therapies.

She also emphasized that all women in this study had undergone conventional breast cancer treatment, including surgery, radiation, chemotherapy, and hormonal therapy. "The aspirin they took was not a substitute for these therapies, it was on top of these therapies," she said. "It is also important to understand that aspirin intake can have detrimental side effects, such as gastrointestinal bleeding."

To prove that aspirin can improve survival in women with breast cancer and to ultimately change clinical practice would require a clinical trial, Dr. Holmes added. "However, women with breast cancer who are already advised by their doctors to take aspirin for another reason might take comfort in the fact that the aspirin might also be preventing recurrence of their breast cancer."

Previous Studies Inconclusive

Experimental studies have shown that aspirin can inhibit growth and decrease the invasiveness of breast cancer cells, reduce cytokines involved in bony metastasis, and stimulate immune responsiveness, the authors write. In addition, meta-analyses of aspirin or other nonsteroidal anti-inflammatory drugs have shown a 9% to 30% reduced risk for breast cancer incidence associated with their use. However, the authors note that the association between aspirin use and breast cancer incidence remains inconclusive.

In the current study, the authors hypothesized that aspirin use after a diagnosis of breast cancer would be associated with both a lower risk for breast-cancer-related death and distant recurrence among women with stage?I to III disease.

They conducted a prospective observational study involving 4164 female participants in the Nurses' Health Study (NHS) who were diagnosed with stages?I, II, or III breast cancer between 1976 and 2002. The women were observed until June 2006 or their death, whichever came first.

Within this cohort, there were 341 breast-cancer-related deaths, 400 distant recurrences (including the 341 breast cancer deaths), and 732 deaths from other causes. A total of 2910 women diagnosed with breast cancer did not provide an aspirin assessment after their diagnosis.

The primary outcome was breast cancer mortality risk according to the number of days per week of aspirin use (0, 1, 2 to 5, or 6 or 7 days), which were assessed at least 12 months after their diagnosis and then updated accordingly.

We measured their aspirin intake after their breast cancer diagnosis.

"We measured their aspirin intake after their breast cancer diagnosis, being careful not to assess their aspirin intake in the first year after their diagnosis when they might have been getting radiation and chemotherapy, when patients are advised not to take aspirin," said Dr. Holmes.

Their results showed that aspirin use was associated with a decreased risk for breast cancer death, and the results did not appreciably differ when they were stratified by disease stage, body-mass index, menopausal status, or estrogen-receptor status. The results were all the "more notable" because the NHS failed to find an association between aspirin use and breast cancer incidence, say the authors.

Compared with never users, the multivariate adjusted relative risks (RRs) for breast cancer mortality were:

0.88 (95% confidence interval [CI], 0.64?- 1.22) for past use
1.07 (95% CI, 0.70?- 1.63) for current use 1 day per week
0.29 (95% CI, 0.16- 0.52), for current use 2 to 5 days per week
0.36 (95% CI, 0.24?- 0.54) for current use 6 or 7 days per week.
The results were similar for distant recurrence; adjusted RRs were 0.91 (95% CI, 0.62?- 1.33), 0.40 (95% CI, 0.24?- 0.65), and 0.57 (95% CI, 0.39?- 0.82) for 1, 2 to 5, and 6 or 7 days of aspirin use, respectively.

In addition, aspirin use was associated with a decreased risk for mortality from any cause; multivariate RRs for overall mortality were 0.96 (95% CI, 0.76?- 1.21), 0.94 (95% CI, 0.67?- 1.32), 0.53 (95% CI, 0.37?- 0.76), and 0.54 (95% CI, 0.41- 0.70) for past, current 1 day per week, current 2 to 5 days per week, and current 6 or 7 days per week of use, respectively.

For all-cause mortality, the authors note that the protective effect associated with aspirin appears to be "driven by the impact on breast cancer death."

They speculate that the association between breast cancer death and aspirin use was stronger than with recurrence, "because recurrence is more likely to be misclassified than death." There was also a "modest association" with the duration of aspirin use, and the authors note that aspirin use "may influence proximal rather than distal events in the cancer pathway."

"If confirmed, our results may broaden the scope of interventions available to reduce breast-cancer-related morbidity and mortality," they conclude.

The study was supported by a grant from the National Institutes of Health. The authors have disclosed no relevant financial relationships.

J Clin Oncol. Published online February?16, 2010.