現在可以更早發現侵犯性乳癌


  【24drs.com】根據第4屆美國癌症研究協會(AACR)、癌症健康跨科科學(SCHD)研討會中的研究結果,現在可以在癌症細胞出現前即檢測年輕高風險非裔美國女性的乳癌。
  
  杜克大學乳癌與卵巢癌計劃共同主席Victoria L. Seewaldt醫師指出,研究的新進展是,我們可以在癌前細胞就發現三重陰性乳癌的存在,我們需要做前瞻試驗,這個檢測有助於我們釐清具有惡化高風險的癌前病變。
  
  研究試圖探討婦女發生侵犯性乳癌之前的變化,研究對象是兩組分別有39和38人的非裔美國籍高風險停經婦女,這些高風險婦女的母親或姐妹在年輕時即死於乳癌。
  
  許多早期惡化的病患向Seewaldt醫師表示,她們的乳癌似乎憑空出現。案例之一,病患的磁振造影診斷時是正常的,6個月時,看起來不對勁,12個月時,這名婦女患有兩處三重陰性乳癌。
  
  研究人員假設,或許可能可以在發生時、在侵犯性乳癌出現前就偵測到侵犯性表現型;他們可以發現非典型、異常表現、和發展成侵犯性乳癌有高度可能性的細胞,但是研究者真正想要知道有哪個訊息路徑可以被活化。
  
  小樣本分析蛋白質的存在之後,他們列出包括AKT/mTOR 在內的三種活化類型,AKT/mTOR是一種在侵犯性三重陰性乳癌中被活化的癌症訊息路徑。
  
  Seewaldt醫師表示,這出現了所謂的瓦氏效應,根據這個現象,就算有氧氣存在,侵犯性癌細胞吞噬了葡萄糖且變得適應,這是侵犯性癌症的指標行為。
  
  研究人員假設,他們可以使用瓦氏效應中的葡萄糖攝取作為及早發現的生物標記,且可作為治療標靶。
  
  他們發現非典型胸部細胞的高度葡萄糖攝取之後,回頭找他們的社區夥伴提議一個臨床試驗,檢測標靶抑制劑;但是社區的婦女不願意參加臨床試驗,因為無法負擔用於預防的藥物。
  
  此外,在糖尿病、心臟病、高血壓、肥胖盛行的區域中,婦女想要有益心臟健康的預防方法,而不是要tamoxifen這類會增加中風或心臟病風險的藥物,研究者只好重新設計。
  
  為了將這篇研究付諸治療,Seewaldt醫師指出,胰島素刺激了AKT/mTOR這個已知的模擬癌症受體路徑。如果未治療,有些前期糖尿病或糖尿病患者,會刺激癌前細胞與促使轉為癌細胞。但是,減重、運動與服用metformin (這些方法都會影響葡萄糖和胰島素活性)可抑制非典型細胞的生長。她指出,metformin是一個用於糖尿病的老藥,可使胰島素分泌下降,每月花費僅4美元。
  
  Seewaldt醫師指出,研究結果使得可以設計小型、便宜的快速試驗。如果知道生物學上的機轉,就可以媒合預防藥物和精準檢測個別婦女服用藥物後的細胞反應。這個方法可讓研究者檢測50-100名婦女在12個月期間內的用藥,可以進行數百個試驗檢測併用metformin加上運動、飲食控制等的效果,且精準測量結果。
  
  George Washington大學癌症研究中心執行主任、分子與細胞腫瘤計畫主任Steven Patierno博士表示,事實上,她參與了社區的整個演變,這是科學和社區合作的最佳範例,且實際上有重要發現,也改變了我們探討某些疾病與如何治療的面向。
  
  這是順著直覺的好例子,注意實際的資料,之後客觀地做出反應,做出這些漸進式的步驟且獲得新的觀察,可幫助我們釐清為何高度侵犯性的乳癌只對部分人有害。
  
  資料來源:http://www.24drs.com/professional/list/content.asp?x_logon=W&x_idno=6616&x_classno=0
  

Earlier Detection of Aggressive Breast Cancer Now Possible

By Sandra Yin
Medscape Medical News

September 20, 2011 (Washington, DC) — It’s now possible to test for breast cancers in young, high-risk African-American women before cancer cells appear, according to study results presented Monday at the Fourth American Association for Cancer Research (AACR) Conference on the Science of Cancer Health Disparities (SCHD).

"What’s new about our study is that we can find activation of some of the things that are bad in triple-negative breast cancer in precancerous cells," investigator Victoria L. Seewaldt, MD, told Medscape Medical News. She is professor of medicine and co-director of the breast and ovarian cancer program at Duke University in Durham, North Carolina.

"We need to do prospective testing," she said, "but we think we have a promising test that might be able to help us sort out precancers that are at high risk of progressing."

The researchers sought to study what happens before a woman develops an invasive breast cancer. They looked at 2 groups of 39 and 38 high-risk premenopausal African-American women. These high-risk women typically had mothers or sisters who died of breast cancer at an early age.

Many patients who got earlier, accelerated breast cancer told Dr. Seewaldt their breast cancer seemed to come out of nowhere. In 1 case, the patient's magnetic resonance image was normal at diagnosis. At 6 months, it looked "busy." At 12 months, the woman had 2 triple-negative breast cancers.

The researchers hypothesized it might be possible to detect the aggressive phenotype at onset, before invasive breast cancer set in. They were able to find atypia, or abnormally behaving cells associated with a higher likelihood of developing into invasive breast cancer, but the investigators really wanted to get at what signaling pathways might be activated.

After profiling small samples for the presence of proteins, they spotted 3 activation patterns, including AKT/mTOR, a cancer signaling pathway activated in aggressive triple-negative breast cancer.

That’s where the Warburg effect comes in. According to the phenomenon, even in the presence of oxygen, aggressive cancer cells devour glucose and become addicted to it, Dr. Seewaldt said, behavior that is a hallmark of aggressive cancers.

The researchers hypothesized that they would be able to use the glucose uptake of the Warburg effect as a biomarker for early detection and as a therapy target.

After they found atypical mammary cells with high glucose uptake, they went back to their community partners and suggested a clinical trial that would test targeted inhibitors. But the women in the community were not willing to take part in a clinical trial that would lead to an unaffordable drug being used for prevention.

Also, in an area where diabetes, heart disease, hypertension, and obesity are common, women wanted heart-healthy prevention and were not open to something like tamoxifen that would lead to increased stroke and possibly heart disease. The researchers went back to drawing board.

To translate the study into therapy, Dr. Seewaldt noted that insulin stimulates AKT/mTOR, the receptor pathway known to simulate cancer. If untreated, someone with prediabetes or diabetes, in which the body produces more sugar, might stimulate precancerous cells and promote a conversion to cancer cells every time they ate. But weight loss, exercise, and metformin (all of which affect glucose and insulin activity) would inhibit the growth of the atypical cells, she said. She pointed out that metformin is an old diabetes drug that drives insulin production down and costs $4 a month.

The study findings make it possible to devise small, cheap, fast trials, Seewaldt said. If one knows the biology ahead of time, one can match the biology with the prevention drug and measure precisely what is happening in an individual woman’s cells when she takes that drug. This approach would allow researchers to test drugs using 50 to 100 women over 12 months. They could run hundreds of trials testing combinations such as a heart-healthy regimen such as metformin plus exercise plus diet and precisely measure the outcome.

Steven Patierno, PhD, who is executive director of the George Washington University Cancer Institute, Washington, DC, and director of the molecular and cellular oncology program, told Medscape Medical News he found Dr. Seewaldt’s presentation fascinating.

"The fact that she involved the community in the evolution of the discovery I think is a great example of how science and community partners can walk in lockstep together, and actually make discoveries that are important and might change the face of how we look at certain diseases and how we treat certain diseases," Dr. Patierno said.

It’s a great example of just following your nose, he added, paying attention to what the data actually say and then reacting to them objectively and making these incremental steps that led to a novel observation that might help us figure out why highly aggressive breast cancer strikes some people and not others.

Dr. Victoria Seewaldt has disclosed no relevant financial relationships. Dr. Patierno has financial relationships with the American Cancer Society, Avon, CC, Washington DC Department of Health, EUSA Pharmaceuticals, Metastatin Pharmaceuticals, National Institutes of Health, PalliaTech Inc., Pfizer Inc., and Theralogix Inc.

Fourth American Association for Cancer Research (AACR) Conference on the Science of Cancer Health Disparities (SCHD); Abstract #B89. Presented September 19, 2011.

    
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