芳香酶抑制劑:對治療癌症有幫助,但有心臟風險?


  【24drs.com】根據發表於2016年聖安東尼奧乳癌研討會(San Antonio Breast Cancer Symposium,SABCS)的一篇小型研究,內皮功能障礙,是心臟病預測因子,也是用於治療停經婦女乳癌之芳香酶抑制劑(AI)的副作用之一。
  
  研究作者、明尼亞波里明尼蘇達大學血液腫瘤科副教授Anne H. Blaes醫師表示,但是,這些研究結果不應該改變適當的乳癌處置,至少在最初期時。
  
  她認為,乳癌治療的最初5年中,我肯定不會推薦不同的方法。我們知道,使用芳香酶抑制劑有存活優勢和無病存活優勢。我認為,這意味著,我們要妥善管理其他風險因素,如高血壓、高血脂和抽菸,而不是忘記它們。
  
  但是,隨著延長AI治療,這議題越來越模糊且事實上是一個備受爭議的問題。
  
  新的橫斷面研究比較了36名停經婦女(平均年齡61歲)、處方有AI用於其局部晚期乳癌的治癒意圖治療,以及對照組的20名健康停經婦女(平均年齡59歲)。
  
  乳癌患者中,約半數(48.6%)曾接受化療、67.7%曾接受放射線治療,對於曾接受AI者,大部份是服用letrozole (44.1%)或 anastrozole (41.2%),14.7%使用exemestane,只有7%曾使用tamoxifen。
  
  研究者使用EndoPAT測量參與者的小動脈、大動脈彈性發現,病例組的彈性比對照組降低,校正收縮壓的差異之後亦然,案例組患者的EdoPAT比率顯著降低(0.8 vs 2.7) ─ 內皮功能障礙的指標(P < .00101)。
  
  她指出,根據EndoPAT比率測定,絕大多數參與者的心臟風險增加,如依據Framingham風險分數則不會被視為有風險。
  
  關於婦女是否接受化療、放射治療或左側或右側癌症,血管功能似乎沒有差異。使用AI者中,相較於exemestane和letrozole,anastrozole與大動脈彈性顯著大幅降低有關。她表示,使用的AI時間長短與比率之間沒有關聯。
  
  不出所料,相較於對照組,以AI治療的婦女,estradiol數值顯著較低(2 vs 15 pg/mL)。
  
  她結論指出,鑑於這些女性可因優秀的治療法延長壽命,我們必須了解這些治療處方的長期併發症,隨著內分泌治療所需時間延長的趨勢,我認為,當我們沒有看到整體存活優勢時,我們真的需要考慮潛在的風險。
  
  加州大學洛杉磯分校的Patricia A. Ganz醫師在會議討論時,形容這些是令人振奮且產生假設的研究結果,當比較具有不同estradiol值的女性時,觀察結果真正適合我們對內皮功能方面的生理期望。
  
  她認為,在AI治療開始前後,進行前瞻性評估以探討誰的風險比較高,將會非常重要;並補充道,這對於停經前婦女也可能非常重要。
  
  她表示,這些婦女治癒乳癌之後,可望存活30或40年,我們當然會擔心這群年輕女性各種相互影響的死亡因素。
  
  資料來源:http://www.24drs.com/
  
  Native link:Aromatase Inhibitors: Is Cancer Benefit Worth Cardiac Risk?

Aromatase Inhibitors: Is Cancer Benefit Worth Cardiac Risk?

By Kate Johnson
Medscape Medical News

SAN ANTONIO — Endothelial dysfunction, a predictor of cardiac disease, may be a side effect of aromatase inhibitor (AI) therapy among postmenopausal women with breast cancer, according to results from a small study reported at the San Antonio Breast Cancer Symposium (SABCS) 2016.

But the findings should not alter appropriate breast cancer management, at least initially, said investigator Anne H. Blaes, MD, associate professor of hematology and oncology at the University of Minnesota, in Minneapolis.

"I think in the first 5 years of breast cancer treatment, for sure I wouldn't recommend something different," she told Medscape Medical News. "We know there's a survival advantage and a disease-free survival advantage from using aromatase inhibitors. I do think it means we have to manage other risk factors, such as high blood pressure, high lipid profile, and tobacco use, very well instead of forgetting about them."

But with extended AI therapy, this issue is less clear and is in fact a much-debated question, she noted.

The new cross-sectional study compared 36 postmenopausal women (mean age, 61 years) who had been prescribed an AI for curative-intent treatment of their locally advanced breast cancer and 20 healthy postmenopausal women who served as controls (mean age, 59 years).

Among the breast cancer patients, about half (48.6%) had received chemotherapy and 67.7% had received radiation. For those who had received AIs, most had received either letrozole (44.1%) or anastrozole (41.2%), with 14.7% having received exemestane. Only 7% had received tamoxifen.

The study found that small- and large-artery elasticity, measured via EndoPAT testing, was reduced among case patients compared to control persons, even after adjustment for differences in systolic blood pressure, resulting in a significantly lower EdoPAT ratio for case patients (0.8 vs 2.7) ─ an indication of endothelial dysfunction (P < .00101).

The vast majority of participants who had increased cardiac risk, as determined on the basis of EndoPAT ratio levels, would not have been considered at risk on the basis of Framingham Risk Scores, she noted.

Vascular function did not seem to differ with respect to whether women had received chemotherapy, radiation, or had left- or right-sided cancer. Among the AIs, anastrozole was associated with a significantly greater reduction in large-artery elasticity in comparison with exemestane and letrozole. "There was no association between length of time on an AI and EndoPAT ratio," she said.

Not surprisigingly, median estradiol levels were significantly lower in AI-treated women compared to control persons (2 vs 15 pg/mL).

"Given these women live longer due to excellent therapies, it's imperative that we have an understanding of the long-term complications of these prescribed therapies," she concluded. "With the growing trend that longer duration of endocrine therapy is needed, I think we really need to take into consideration the potential risks when we're not seeing overall survival advantages."

Calling the findings "provocative" and "hypothesis-generating," Patricia A. Ganz, MD, session discussant from the University California, Los Angeles, said the observations "really fit with what we would expect the physiology to be in terms of endothelial function when comparing women with differing levels of estradiol."

She suggested that "prospective evaluation is going to be very important before and after initiation of AI therapy to see who might be at higher risk," adding that this might also be very important in premenopausal women as well.

"These are women who are going to live 30 or 40 years after being cured of their breast cancer, and we certainly have to worry about this competing cause of death in this group of younger women," she said.

The study was funded by a grant from the National Institutes of Health and a Masonic Scholar Award. Dr Blaes and Dr Ganz have disclosed no relevant financial relationships.

San Antonio Breast Cancer Symposium (SABCS) 2016: Abstract S5-07. Presented December 9, 2016.

    
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