芳香酶抑制剂:对治疗癌症有帮助,但有心脏风险?


  【24drs.com】根据发表于2016年圣安东尼奥乳癌研讨会(San Antonio Breast Cancer Symposium,SABCS)的一篇小型研究,内皮功能障碍,是心脏病预测因子,也是用于治疗停经妇女乳癌之芳香酶抑制剂(AI)的副作用之一。
  
  研究作者、明尼亚波里明尼苏达大学血液肿瘤科副教授Anne H. Blaes医师表示,但是,这些研究结果不应该改变适当的乳癌处置,至少在最初期时。
  
  她认为,乳癌治疗的最初5年中,我肯定不会推荐不同的方法。我们知道,使用芳香酶抑制剂有存活优势和无病存活优势。我认为,这意味著,我们要妥善管理其它风险因素,如高血压、高血脂和抽菸,而不是忘记它们。
  
  但是,随著延长AI治疗,这议题越来越模糊且事实上是一个备受争议的问题。
  
  新的横断面研究比较了36名停经妇女(平均年龄61岁)、处方有AI用于其局部晚期乳癌的治癒意图治疗,以及对照组的20名健康停经妇女(平均年龄59岁)。
  
  乳癌患者中,约半数(48.6%)曾接受化疗、67.7%曾接受放射线治疗,对于曾接受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测量参与者的小动脉、大动脉弹性发现,病例组的弹性比对照组降低,校正收缩压的差异之后亦然,案例组患者的EdoPAT比率显著降低(0.8 vs 2.7) ─ 内皮功能障碍的指标(P < .00101)。
  
  她指出,根据EndoPAT比率测定,绝大多数参与者的心脏风险增加,如依据Framingham风险分数则不会被视为有风险。
  
  关于妇女是否接受化疗、放射治疗或左侧或右侧癌症,血管功能似乎没有差异。使用AI者中,相较于exemestane和letrozole,anastrozole与大动脉弹性显著大幅降低有关。她表示,使用的AI时间长短与比率之间没有关联。
  
  不出所料,相较于对照组,以AI治疗的妇女,estradiol数值显著较低(2 vs 15 pg/mL)。
  
  她结论指出,监于这些女性可因优秀的治疗法延长寿命,我们必须了解这些治疗处方的长期并发症,随著内分泌治疗所需时间延长的趋势,我认为,当我们没有看到整体存活优势时,我们真的需要考虑潜在的风险。
  
  加州大学洛杉矶分校的Patricia A. Ganz医师在会议讨论时,形容这些是令人振奋且产生假设的研究结果,当比较具有不同estradiol值的女性时,观察结果真正适合我们对内皮功能方面的生理期望。
  
  她认为,在AI治疗开始前后,进行前瞻性评估以探讨谁的风险比较高,将会非常重要;并补充道,这对于停经前妇女也可能非常重要。
  
  她表示,这些妇女治癒乳癌之后,可望存活30或40年,我们当然会担心这群年轻女性各种相互影响的死亡因素。
  
  资料来源: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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