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June 9, 2008 (芝加哥) — 复发或者转移乳癌的妇女中，病灶复发位置的雌激素受体 (ER)/黄体素受体(PR) 和/或HER2状态，可能和原发肿瘤不同。研究者在美国临床肿瘤医学会第44届年会中报告指出，一大部分(28%)的复发肿瘤ER/PR或HER2状态改变，显示应常规进行复发位置的切片，以决定适当的治疗选择。
温哥华British Columbia大学医学系住院医师Robyn MacFarlane解释，假设乳癌复发位置和原发肿瘤的分子显型应相同；大部分的病患没有进行额外的切片，如果显型有所不同，我们或许需要在治疗上有所改变。
最近的小型研究认为，有些乳癌病患中，复发肿瘤的HER2和荷尔蒙受体状态和原本病灶可能不同；这些案例中，对原发癌症有效的治疗选择可能对复发/转移病灶不再适当。
在这个研究中，MacFarlane医师等人比较了复发/转移乳癌和原本肿瘤的ER/PR与HER2受体状态，使用大型的族群基础资料库和组织晶片(TMA)分析；研究者定义BCOU(British Columbia Cancer Agency Breast Cancer Outcomes Unit)资料库中，于1986至1992年间切片证实复发的妇女的资料 。
此资料库中的原发乳癌病患且目前有大型TMA系列检查的妇女，共4,444人，回顾病历之后，研究者要求取得复发/转移癌症的组织块，对复发/转移肿瘤进行第二次的TMA系列检查。
BCOU资料库中，281个案例与TMA系列检查有关，其中，取得184件组织块，全部的病患都有局部、区域或者远端复发，这184件样本中，160件适合进行原发和复发肿瘤的HER2 与PR/ER状态分析。
160件样本中，115件(72%)显示荷尔蒙受体或HER2状态都没有改变，不过，其他45 件肿瘤样本(11%) 的受体状态有所改变，其中11件(7%)有局部复发，另34件 (21%)区域或远端复发。
MacFarlane医师表示，我们看见ER状态从阳性变为阴性，从阴性变为阳性，也发现HER2有同样的变化。
区域或远端复发的34例中：
* 11 例从ER/PR阳性变成ER/PR阴性
* 14 例从 ER/PR 阴性变成 ER/PR 阳性
* 3 例从HER2 阴性变成 HER2 阳性
* 6 例从HER2 阳性变成 HER2 阴性
MacFarlane医师结论表示，已知这是评估原发和复发乳癌之分子显型变化的最大型研究，结果显示，应常规进行转移/复发乳癌切片；她指出，复发病灶的切片是适当治疗的重要因素，须对该组织进行进一步的研究。
麻州综合医院乳癌研究主任Paul E. Goss医师在此研究的讨论会中表示，本研究提出三种临床使用的生物标记，这些在目前用于治疗选择；眼前的问题是，原发肿瘤到复发之间是否有生物演化，如果有，这些变化会不会影响治疗？
Goss医师解释，这项研究有其研究限制，我们应将此视为议题的开端而非结束，这个研究是回溯型，样本数也少，因此还难以下定论，而且还有取样错误的问题。
另一个考量因素是样本位置，不同的转移位置会显示出状态的变化；同时，研究资料局限在ER、PR和HER2，未分析其他路径；最后，一个重要问题是，样本取自接受多元辅助治疗者。
不过，他表示，这项研究指出评估原发和转移肿瘤变化的重要性，我们需要有适当的科技确认这些变化，需要以前溯式方式确认生物发现和后续治疗反应之间的关联。
美国临床肿瘤医学会(ASCO)第44届年会：摘要1000 摘要 。发表于2008年6月2日。
Molecular Phenotypes in Breast Cancer May Differ Between Primary Tumor and Sites of Recurrence
By Roxanne Nelson
Medscape Medical News
June 9, 2008 (Chicago, Illinois) — Among women with relapsed or metastatic breast cancer, the sites of cancer recurrence might have an estrogen-receptor (ER)/progesterone-receptor (PR) and/or HER2 status that is different than the primary tumor. Researchers here at the American Society of Clinical Oncology 44th Annual Meeting reported that a significant proportion (28%) of relapsed tumors had changes in either ER/PR or HER2-receptor status, and suggested that biopsies of relapsed sites should routinely be performed to determine optimal treatment options.
It has been assumed that sites of relapse are the same phenotypes as the primary tumor in breast cancer, explained Robyn MacFarlane, MD, a resident in the department of medicine at the University of British Columbia, in Vancouver.
"Most patients do not have additional biopsies performed," she said. "If there are differences in the phenotypes, we may need to make changes in treatment."
Recent small studies have suggested that, in some breast cancer patients, the HER2- and hormone-receptor status of the relapsed tumor can be different than the status of the original lesion. In those cases, treatment options that were effective in the primary cancer might no longer be optimal for the relapsed/metastatic disease.
In this study, Dr. MacFarlane and colleagues compared the ER/PR and HER2-receptor status of relapsed/metastatic breast cancer tumors with the status of the original tumor, using a large population-based database and tissue microarray (TMA) cohort. The researchers identified women from the British Columbia Cancer Agency Breast Cancer Outcomes Unit (BCOU) database who experienced biopsy-proven relapses between 1986 and 1992.
The women identified from the database were associated with a current large TMA series (n?= 4444) of primary breast cancers. After conducting a chart review, the researchers requested available tissue blocks of the relapsed/metastatic cancers. A secondary TMA series was created from the relapsed/metastatic tumors.
From the BCOU database, 281 cases were linked to the TMA series; of these, 184 tissue blocks were available. All patients had experienced a local, regional, or distant relapse of their breast cancer and, of the 184 samples, 160 were adequate for analysis of HER2 and PR/ER status of both the primary and relapsed tumors.
In all, 115 of the 160 samples (72%) showed no change in either hormone-receptor or HER2 status. However, the remaining 45 tumor samples (11%) did exhibit changes in receptor status. Eleven (7%) of these were local recurrences and 34 (21%) were regional or distant relapses.
"We saw changes in ER status from positive to negative and from negative to positive, and we also saw the same shift for HER2," said Dr. MacFarlane.
Among the 34 regional/distant relapses:
11 changed from ER/PR positive to ER/PR negative
14 changed from ER/PR negative to ER/PR positive
3 changed from HER2 negative to HER2 positive
6 changed from HER2 positive to HER2 negative.
"This is one of the largest known studies to assess changes in molecular phenotype between the primary and relapsed breast cancer," concluded Dr. MacFarlane. "And the results suggest that biopsies of relapsed/metastatic breast cancers should be performed routinely."
Obtaining biopsies of recurrent sites could be an important factor in optimizing treatment, she added, and further study of this issue is warranted.
"This study address 3 of the biomarkers used in the clinic, which currently guide our choice of treatment," said Paul E. Goss, MD, PhD, director of Breast Cancer Research at Massachusetts General Hospital, in Boston, in a discussion of the study. "The question put before us is whether there is biologic evolution from the primary tumor to relapse. If so, should these changes guide the treatment?"
Dr. Goss explained that although there are limitations to this study, we should view this as the beginning of the debate and not the end. "The study was retrospective and the sample size was small, and that makes it difficult to draw conclusions," he said. "There is also the issue of sampling errors."
Another factor to consider is the site of the sample; the different sites of metastases could show variations in status. Also, the data were restricted to ER, PR, and HER2, and no other pathways were analyzed. Finally, a critical issue is that the samples were taken after multiple adjuvant therapy.
However, this study has highlighted the importance of evaluating changes between primary and metastatic tumors. "We need to optimize the technologies available to verify these changes, and we need to prospectively correlate any biologic findings with subsequent response to treatment," he said.
American Society of Clinical Oncology (ASCO) 44th Annual Meeting: Abstract 1000. Presented June 2, 2008.