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【資源】當(dāng)乳腺癌發(fā)生轉(zhuǎn)移時(shí)，腫瘤生物特性如ER,PR,HER2可能發(fā)生改變
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June 10, 2010 (Chicago, Illinois) — For breast cancer patients whose disease has metastasized, tumor biology often changes between primary and metastatic lesions. According to the results of a retrospective study presented here at the American Society of Clinical Oncology 2010 Annual Meeting, a proportion of women with metastatic breast cancer required a change in therapy after rebiopsy revealed discordance in receptor status between the primary tumor and liver metastasis. The authors found that estrogen-receptor (ER), progesterone-receptor (PgR), or HER2-receptor status of liver metastases differed from that of the primary breast tumor, necessitating a change in endocrine therapy or targeted treatment in 12.1% of the study cohort. "There is emerging evidence that tumor receptor status may change dynamically during the natural history of the disease," said lead author Marzia Locatelli, MD, during her presentation. Dr. Locatelli, who is from the European Institute of Oncology in Milan, Italy, added that when it is "safe and easy to perform, a biopsy of the metastatic lesion should be considered in all patients, particularly if there is a long interval from diagnosis to biopsy." Possible Reasons and Questions for the Future There are any number of reasons for the discordance seen in the primary tumor and metastatic lesions, said Andrea L. Richardson, MD, PhD, who served as a discussant of the paper. Errors in assay methodology is one possible reason, although that would not explain the majority of discordances, said Dr. Richardson, who is assistant professor of pathology at Harvard Medical School in Boston, Massachusetts. Sampling size is another possibility; liver biopsies provide a much smaller sample of tissue for evaluation of ER and PgR status, but Dr. Richardson pointed out that discordance rates for loss of ER or gain of ER are roughly the same, or even a little higher for ER gain in liver metastases. "This suggests that the smaller sample size of recurrences is not the major reason for discordance," she said. A third possibility is delayed fixation and false negative results for the primary tumor, which could explain some of the gain of ER in recurrence. "I think we should be aware of this when thinking about the use of adjuvant therapy, and reducing false negatives on primary tumors as well," Dr. Richardson explained. There might also be biologic reasons for discordance; genomic studies have shown that there is heterogeneity within most tumors. She noted that receptor studies are generally performed only on a single block of the primary breast tumor or limited to a core biopsy of the tumor. "The failure to detect a significant subpopulation with different receptor expression within a large primary tumor may explain discordances," she said, and questioned whether there is an association between tumor size and the likelihood of discordance. "Should we, as pathologists, be evaluating more areas of the primary tumors to rule out a subpopulation with a different phenotype?" she asked. We need to treat the tumor that is present now, not the tumor that used to be there years before. All things considered, the reason for discordance might not be important. "Therapy is determined by receptor status, and we need to treat the tumor that is present now, not the tumor that used to be there years before," Dr. Richardson said. Biopsy of presumed metastatic disease will detect some benign lesions, new primaries, and metastases of a second cancer — all of which require different considerations for treatment and prognosis, Dr. Richardson noted. But this does pose questions for the future, she told the audience. "Is there a subgroup with a low enough rate of discordance to suggest that rebiopsy is not necessary?" "How do ER discordance rates vary based on expression of HER2?" she asked. "Are most of the cases with unstable expression of ER, either gains or losses, occurring in patients with HER2-positive primary tumors?" Discordance Noted, Therapy Changed During a press conference at which the results were highlighted, study coauthor Giuseppe Curigliano, MD, PhD, also from the European Institute of Oncology, pointed out that the premise of this study was very simple: Should liver metastasis or any metastatic site in breast cancer be biopsied to improve treatment choice? "Determination of ER, PgR, and HER2 status is clinically relevant for the treatment choice and for breast cancer subtype determination," he said. "But despite this evidence, it is not routine practice to perform biopsies on metastatic deposits of disease. So when we choose treatments for patients with metastatic disease, we choose the treatment according to the biologic features of the primary tumor." In this study, the authors analyzed a database of ultrasound-guided liver biopsies performed from 1995 to 2008, and identified 255 breast cancer patients with matched primary and liver tissue samples. The median time from primary diagnosis to liver biopsy was 3.4 years (range, 0 to 18.3 years). The overall discordance rate for ER status between the primary tumor and liver metastases was 14.5%. The status of 15 patients (25.9%) changed from ER negative to ER positive, and of 22 patients (11.2%) changed from ER positive to ER negative. For HER2, the authors observed an overall discordance rate of 13.9%. There were 7 patients (5.9%) in whom status switched from HER2 negative to HER2 positive, and 17 patients (31.5%) in whom it changed from HER2 positive to HER2 negative. Progesterone status changed in 48.6% of the patients, and changes in therapy were made in 12.1% of patients on the basis of the results of their liver biopsy. Biopsy More Necessary in Era of Targeted Therapy Other studies have already shown that tumor biology can change. One study, for example, showed that half of cancers change when they spread to the sentinel node. Biopsy of metastases is becoming increasingly more common in the United States, and is being done more and more frequently, said Eric P. Winer, MD, professor of medicine at Harvard Medical School. Certain features of the cancer may be more prominently expressed. Dr. Winer, who moderated the press briefing, noted that with a whole new generation of targeted therapies becoming available over the next decade, "I think that it will be that much more necessary to obtain tissue, not just when a woman first has metastatic breast cancer, but potentially over the course of her illness." "There is the potential that the cancer can evolve over time; it may not actually change, but certain features of the cancer may be more prominently expressed," he added. The authors have disclosed no relevant financial relationships. American Society of Clinical Oncology (ASCO) 2010 Annual Meeting: Abstract CRA1008. Presented June 5, 2010. http://www.dxy.cn/bbs/post/view?bid=116&id=17427513&tpg=1&ppg=1&sty=1#17589917 |
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2010年6月10日（伊利諾州芝加哥）——對(duì)于已發(fā)生轉(zhuǎn)移的乳腺癌病人來(lái)說(shuō)，原發(fā)灶和轉(zhuǎn)移性病變之間的腫瘤生物學(xué)常發(fā)生變化。 根據(jù)美國(guó)臨床腫瘤學(xué)會(huì)2010年會(huì)上展示的一篇回顧性研究結(jié)果，一部分轉(zhuǎn)移性乳腺癌病人在重新活檢后發(fā)現(xiàn)原發(fā)腫瘤和肝轉(zhuǎn)移灶之間受體狀態(tài)不一致，因而她們需要重新選擇治療方案。 研究人員發(fā)現(xiàn)ER、PR和HER2在肝轉(zhuǎn)移灶和原發(fā)灶之間有差異，根據(jù)該研究人群，有12.1%患者需要在內(nèi)分泌治療或靶向治療發(fā)生變化。 該文的主要作者M(jìn)arzia Locatelli在她的介紹中說(shuō)：“新的證據(jù)表明在疾病自然史中腫瘤受體狀態(tài)可發(fā)生明顯改變�！� 來(lái)自于意大利米蘭的歐洲腫瘤研究所的Locatelli博士補(bǔ)充道：“當(dāng)再次活檢是安全和容易進(jìn)行時(shí)，應(yīng)對(duì)所有病人的轉(zhuǎn)移性病變進(jìn)行活檢，特別是如果距離首次活檢診斷有較長(zhǎng)間隔時(shí)�！� 可能的原因和未來(lái)的問(wèn)題 原發(fā)腫瘤和轉(zhuǎn)移性腫瘤不一致性有許多原因，該文的作者之一Andrea L. Richardson博士說(shuō)。 檢測(cè)方法錯(cuò)誤是其中一個(gè)原因，盡管這不能解釋大多數(shù)不一致性。來(lái)自于曼徹斯特波士頓的哈佛醫(yī)學(xué)院的病理學(xué)助理教授Richardson博士說(shuō)道。 樣本大小是另一個(gè)可能的原因。肝活檢雖提供了很小的標(biāo)本用于ER和PR的檢測(cè)，但Richardson博士指出ER失表達(dá)率和陽(yáng)性率大致是相同的，在肝轉(zhuǎn)移灶中甚至ER陽(yáng)性率略高。她說(shuō)：“這表明復(fù)發(fā)的小標(biāo)本不是結(jié)果不一致的主要原因�！� 第三個(gè)可能的原因是原發(fā)腫瘤延遲固定和假陰性結(jié)果，這個(gè)能解釋復(fù)發(fā)病灶的ER陽(yáng)性表達(dá)。“我認(rèn)為當(dāng)我們考慮輔助治療時(shí)我們應(yīng)知道這個(gè)，也可減少原發(fā)灶的假陰性率�！盧ichardson博士說(shuō)道。 原發(fā)灶和轉(zhuǎn)移灶激素受體不一致性可能還有生物因素，基因組研究顯示大多數(shù)腫瘤內(nèi)存在異質(zhì)性。她指出受體研究基本上是在原發(fā)腫瘤一個(gè)蠟塊上或局限于腫瘤的粗針活檢標(biāo)本中進(jìn)行。 她說(shuō)：“在一個(gè)大的原發(fā)灶內(nèi)未能檢出不同受體表達(dá)的亞群可解釋結(jié)果不一致性�！眴�(wèn)題是腫瘤大小和不一致的可能性之間是否存在相關(guān)性。 她問(wèn)道：“作為病理醫(yī)生，我們應(yīng)該評(píng)價(jià)原發(fā)腫瘤的較多區(qū)域以排除不同表型的亞群�！� 我們需要治療現(xiàn)在存在的腫瘤，而不是3年前的腫瘤。 所有的東西都考慮過(guò)，不一致的原因可能并不重要。Richardson博士說(shuō)道：“治療是由受體狀態(tài)決定的，我們需要治療現(xiàn)在存在的腫瘤，而不是3年前的腫瘤�！� Richardson指出，假定轉(zhuǎn)移灶的活檢將檢出一些良性病變，新的疾病和第二個(gè)癌的轉(zhuǎn)移——所有這些需要考慮選擇不同的治療和評(píng)估病人預(yù)后。 但這個(gè)也會(huì)將來(lái)引發(fā)一些問(wèn)題，她告訴聽(tīng)眾，“有一個(gè)足夠低不一致率的亞群可以提示重新活檢不需要嗎？” ER不一致率如何基于HER2表達(dá)而發(fā)生改變呢？“她問(wèn)道：”大多數(shù)ER不穩(wěn)定表達(dá)的病例，或者獲得或丟失，在HER2陽(yáng)性原發(fā)腫瘤病人也發(fā)生嗎？“ 不一致性應(yīng)注明，治療也會(huì)改變 在該結(jié)果被突出顯示的新聞發(fā)布會(huì)上，該項(xiàng)研究的共同作者，也是歐洲腫瘤研究所的Giuseppe Curigliano博士指出這項(xiàng)研究的前體非常簡(jiǎn)單，那就是乳腺癌肝轉(zhuǎn)移灶和其他任何轉(zhuǎn)移灶被活檢能提高治療選擇嗎？ “ER、PR和HER2表達(dá)狀態(tài)臨床上與治療選擇和乳腺癌亞型有關(guān)，”他說(shuō)：“但是盡管有這個(gè)證據(jù)，但對(duì)轉(zhuǎn)移灶不能常規(guī)進(jìn)行活檢。因此當(dāng)我們對(duì)轉(zhuǎn)移性疾病病人選擇治療方案是，我們根據(jù)原發(fā)腫瘤的生物學(xué)特征而選擇治療方案�！� 在這項(xiàng)研究中，作者分析了1995-2008年間超聲指導(dǎo)下肝活檢的資料，發(fā)現(xiàn)了255例同時(shí)有原發(fā)灶和肝轉(zhuǎn)移灶標(biāo)本的乳腺癌病人。原發(fā)診斷到肝活檢的平均時(shí)間是3.4年（范圍0-18.3年）。 原發(fā)腫瘤和肝轉(zhuǎn)移灶ER不一致率為14.5%。15例（25.9%）病人ER從陰性變?yōu)殛?yáng)性，11例（11.2%）從ER陽(yáng)性變?yōu)殛幮浴?br /> HER2總的不一致率為13.9%。7例（5.9%）病人HER2由陰性變?yōu)殛?yáng)性，17例（31.5%）則有陽(yáng)性變?yōu)殛幮浴?br /> 48.6%病人孕激素發(fā)生改變，其中12.1%病人的治療根據(jù)肝活檢的結(jié)果發(fā)生改變。 靶向治療時(shí)代更需要活檢 我們的結(jié)果已經(jīng)顯示腫瘤生物學(xué)能發(fā)生改變。例如一項(xiàng)研究顯示當(dāng)癌轉(zhuǎn)移到前哨淋巴結(jié)時(shí)有一半癌癥發(fā)生變化。 轉(zhuǎn)移灶活檢在美國(guó)變得越來(lái)越常見(jiàn)，頻率也越來(lái)越多。哈佛大學(xué)醫(yī)學(xué)院醫(yī)學(xué)教授Eric P. Winer博士說(shuō)。 癌癥的某些特征可能更加明顯表達(dá)。 主持新聞發(fā)布會(huì)的Winer博士指出整體新一代靶向治療在以后的十年將變得可行�！拔艺J(rèn)為更有必要取得組織，不僅僅當(dāng)一名女性首次有轉(zhuǎn)移性乳腺癌，而是在其疾病過(guò)程中都應(yīng)有可能�！� 他補(bǔ)充道：“隨著時(shí)間的推移，癌癥有這種惡化的可能性，它實(shí)際上可能不發(fā)生變化，但癌癥的某些特征可更加顯著表達(dá)�！� 作者宣布沒(méi)有相關(guān)財(cái)政資助 |
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