乳房活檢診斷癌症並非總是可靠

Breast biopsies are good at telling the difference between healthy tissue and cancer, but less reliable for identifying more subtle abnormalities, a new study finds.

一項新的研究發現，乳房活檢儘管在分辨健康組織和癌變組織差異的時候相當有效，但要辨別出更細微的異常，這種方式就不太可靠了。

Because of the uncertainty, women whose results fall into the gray zone between normal and malignant — with diagnoses like “atypia” or “ductal carcinoma in situ” — should seek second opinions on their biopsies, researchers say. Misinterpretation can lead women to have surgery and other treatments they do not need, or to miss out on treatments they do need.

研究人員表示，由於存在這樣的不確定性，如果一位女性的活檢結果處於正常和惡性之間的灰色地帶——診斷書中有“異型性”或“導管原位癌”這樣的字眼——她就應該尋求關於活檢結果的第二診斷意見。誤判可能會導致女性接受其實並不需要的手術等治療方法，或者讓她們沒有得到確實需要的治療。

The new findings, reported Tuesday in JAMA, challenge the common belief that a biopsy is the gold standard and will resolve any questions that might arise from an unclear mammogram or ultrasound.

人們普遍認爲活檢是最可靠的標準，可以解決不明朗的乳房X光或超聲波檢查結果提出的任何疑問，而本週二發表在《美國醫學會雜誌》（The Journal of the American Medical Association，簡稱JAMA）上的這項研究結果對這個觀點提出了挑戰。

In the United States, about 1.6 million women a year have breast biopsies; about 20 percent of the tests find cancer. Ten percent identify atypia, a finding that cells inside breast ducts are abnormal but not cancerous. About 60,000 women each year are found to have ductal carcinoma in situ, or D.C.I.S., which also refers to abnormal cells that are confined inside the milk ducts and so are not considered invasive; experts disagree about whether D.C.I.S. is cancer.

在美國，每年約有160萬女性做乳房活檢；約20%的活檢發現存在癌細胞。10%診斷爲異型性，即發現乳房導管內的細胞異常，但沒有發生癌變。每年大約有6萬名女性發現患有導管原位癌（ductal carcinoma in situ，簡稱DCIS）。這同樣指的是異常細胞僅存在於乳管內，因此不具侵襲性。DCIS究竟是否屬於癌症，專家的意見也尚未統一。

“It is often thought that getting the biopsy will give definitive answers, but our study says maybe it won’t,” said Dr. Joann G. Elmore, a professor at the University of Washington School of Medicine in Seattle and the first author of the new study on the accuracy of breast biopsies.

“人們常常認爲，活檢可以給出確切答案，但我們的研究顯示未必如此，”在西雅圖的華盛頓大學醫學院(University of Washington School of Medicine)擔任教授的瓊·G·埃爾莫爾(Joann G. Elmore)說。她是這篇關於乳房活檢準確度的新研究論文的第一作者。

Her team asked pathologists to examine biopsy slides, then compared their diagnoses with those given by a panel of leading experts who had seen the same slides. There were some important differences, especially in the gray zone.

她的團隊請病理醫師查看活檢切片，並讓一個權威專家小組查看相同的切片，然後把病理師和專家小組的診斷結果進行比較。研究發現，二者之間存在一些重大差異，在灰色地帶尤其如此。

An editorial in JAMA called the findings “disconcerting.” It said the study should be a call to action for pathologists and breast cancer scientists to improve the accuracy of biopsy readings, by consulting with one another more often on challenging cases and by creating clearer definitions for various abnormalities so that diagnoses will be more consistent and precise. The editorial also recommended second opinions in ambiguous cases.

JAMA發表了一篇社論稱這個發現“令人不安”，並表示此項研究應該提醒病理醫師和乳腺癌方面的科學家行動起來，提高活檢診斷的準確性，方法是互相討論疑難病例，並對各種異常狀況給出更明確的定義，以便提高診斷的一致性和準確性。社論還建議在遇見模棱兩可的病例時尋求第二診斷意見。

A second opinion usually does not require another biopsy; it means asking one or more additional pathologists to look at the microscope slides made from the first biopsy. Dr. Elmore said doctors could help patients find a pathologist for a second opinion.

第二診斷意見通常不需要再做一次活檢；而是指請另外一位或多位病理醫師查看第一次活檢獲得的顯微鏡切片。埃爾莫爾博士稱，醫生可以幫助患者去找另一位病理醫師，以便獲得第二診斷意見。

A surgeon not involved with the study, Dr. Elisa Port, a co-director of the Dubin Breast Center and the chief of breast surgery at Mount Sinai Hospital in Manhattan, said the research underlined how important it is that biopsies be interpreted by highly experienced pathologists who specialize in breast disease.

埃莉薩·波特博士(Elisa Port)在曼哈頓西奈山醫院(Mount Sinai Hospital)擔任杜賓乳房中心(Dubin Breast Center)的聯合主任兼乳房手術負責人，沒有參與這項研究。她認爲，該研究強調了活檢應由擅長乳房疾病的經驗豐富的病理醫師來解讀的重要性。

“As a surgeon, I only know what to do based on the guidance of my pathologist,” Dr. Port said. “Those people behind the scenes are actually the ones who dictate care.”

“作爲一名外科醫生，我進行治療的依據就是病理醫師的診斷意見，”波特博士說。“這些幕後工作者纔是真正決定治療方案的人。”

In Dr. Elmore’s study, the panel of three expert pathologists examined biopsy slides from 240 women, one slide per case, and came to a consensus about the diagnosis.

埃爾莫爾博士的研究使用了240名女性的乳房活檢切片，每個病例一個切片。由三名病理學專家組成的小組會查看這些切片，並對診斷結果達成共識。

“These were very, very experienced breast pathologists who have written textbooks in the field,” Dr. Elmore said.

“這些病理學家對乳房疾病有非常、非常豐富的經驗，一直在撰寫這個領域的教科書，”埃爾莫爾博士說。

Then the slides were divided into four sets, and 60 slides were sent to each of 115 pathologists in eight states who routinely read breast biopsies. The doctors interpreted the slides and returned them, and the same set was sent to the next pathologist. The study took seven years to complete.

然後，切片被分成四組，每組60個，分別送往8個州的115名在日常工作中對乳房活檢結果進行判斷的病理醫師。他們每一個人都對這組切片做出解讀，然後返還。同一組切片再被送到下一名病理醫師那裏。整項研究歷時七年才完成。

The goal was to find out how the practicing pathologists stacked up against the experts. The task was tougher than actual practice, because in real cases pathologists can consult colleagues about ambiguous findings and ask for additional slides. They could not do so in the study.

研究的目標是找出日常執業的病理醫師與專家的意見有多大差異。這個任務要比一般情況更加困難，因爲在現實工作中，病理醫師遇到疑難病例時可以和同事討論，並且要求提供更多的切片。而在這項研究中，他們不能這樣做。

There was good news and bad news. When it came to invasive cancer — cancer that has begun growing beyond the layer of tissue in which it started, into nearby healthy tissue — the outside pathologists agreed with the experts in 96 percent of the interpretations, which Dr. Elmore called reassuring. They found the vast majority of the cancers.

研究結果表明，好消息與壞消息並存。當出現侵襲性癌症時——癌細胞已經超出最初生長的組織層，發展到了附近的健康組織中——日常執業的病理醫師和專家的意見吻合度達96%。埃爾莫爾博士說這一結果讓人感到安心。絕大多數的癌症都被他們發現了。

For completely benign findings, the outside pathologists matched the experts in 87 percent of the readings, but misdiagnosed 13 percent of healthy ones as abnormal.

對於完全良性的病例，日常執業的病理醫師與專家的意見吻合度爲87%，但他們把13%的健康切片誤判爲異常。

The next two categories occupied the gray zone. One was D.C.I.S. For this condition, the pathologists agreed with the experts on 84 percent of the cases. But they missed 13 percent of cases that the experts had found, and diagnosed D.C.I.S. in 3 percent of the readings where the experts had ruled it out.

接下來的兩個類別則屬於灰色地帶。第一個是DCIS。對於這種情況，日常執業的病理醫師和專家的意見吻合度爲84%。不過，有13%的病例經專家發現存在DCIS，但醫師沒有看出來；還有3%的病例被專家認爲不存在DCIS，卻被他們判斷爲存在。

The finding is of concern, because D.C.I.S. sometimes becomes invasive cancer, and it is often treated like an early-stage cancer, with surgery and radiation. Missing the diagnosis can leave a woman at increased risk for cancer — but calling something D.C.I.S. when it is not can result in needless tests and treatments.

這一發現令人擔憂，因爲DCIS有時會發展成侵襲性癌症，而且通常被當成早期癌症在治療，會動用手術和化療手段。沒有判斷出實際存在的DCIS，可能會增加女性的患癌風險——但誤判沒有DCIS的病例的話，則會導致不必要的檢查和治療。

The second finding in the gray zone was atypia, in which abnormal, but not cancerous, cells are found in breast ducts. Women with atypia have an increased risk of breast cancer, and some researchers recommend surgery to remove the abnormal tissue, as well as intensified screening and drugs to lower the risk of breast cancer.

灰色地帶的第二個發現涉及異型性，即乳房導管裏發現了異常但並未癌變的細胞。這類女性患乳腺癌的風險會有所上升，除了通過加強篩查和使用藥物來降低罹患乳腺癌的風險之外，一些研究者還建議用手術來去除異常組織。

But in the study, the outside pathologists and the experts agreed on atypia in only 48 percent of the interpretations. The outside pathologists diagnosed atypia in 17 percent of the readings where the experts had not, and missed it in 35 percent where the experts saw it.

這項研究發現，在異型性方面，日常執業的病理醫師和專家的判斷只有48%的吻合度。有17%的病例專家認爲不存在異型性，卻被醫師判斷爲存在；還有35%的病例專家認爲存在異型性，但醫師並沒有發現。

“Women with atypia and D.C.I.S. need to stop and realize it’s not the same thing as invasive cancer, and they have time to stop and reflect and think about it, and ask for a second opinion,” Dr. Elmore said.

“有異型性和DCIS的女性不要匆忙採取行動，而是要認識到它們和侵襲性癌症不是一回事。她們有時間停下來考慮一下，想想這件事，尋求第二診斷意見，”埃爾莫爾博士說。

Abby Howell, 57, who lives in Seattle, two years ago had some calcifications show up on a mammogram, which are sometimes a sign of cancer. She was given the option of just mammograms every six months or having a biopsy. She chose the biopsy, thinking it would be definitive. But instead, it showed atypia.

57歲的艾比·豪厄爾(Abby Howell)住在西雅圖。兩年前， X光檢查顯示她的乳房有鈣化現象，而有時這是癌症的徵兆。她可以選擇簡單地每半年做一次乳房X光檢查，也可以選擇做活檢。她選擇了後者，以爲活檢結果會明確無誤。但檢查結果爲異型性。

Ms. Howell, who has a master’s degree in public health, looked up the condition and realized it was unclear whether those odd-looking cells would ever lead to cancer. Surgery was recommended, but she decided to watch and wait instead. So far, her mammograms have been normal, but the experience has shaken her peace of mind.

豪厄爾擁有公共衛生碩士學位，她瞭解了一下情況，發現目前還不清楚這些異常細胞會不會導致癌症。醫生建議手術治療，但她決定觀望等待。迄今爲止，她的乳房X光檢查結果一直正常，但這段經歷讓她感到心裏不踏實。

“If I had to do it all over again, I wouldn’t have jumped for the biopsy,” Ms. Howell said. “I really regret it. In a way it’s made more anxiety in my life.”

“如果不得不再來一遍的話，我就不會匆忙選擇活檢了，”豪厄爾說。“我真的很後悔。從某種程度上說，這給我的生活帶來了更多的焦慮感。”