若年輕時有接受胸部X光 則建議進行乳癌監測
作者：Nick Mulcahy
出處：WebMD醫學新聞
April 6, 2010 — 根據一篇新的系統性回顧，在童年、青春期或青年時接受胸部放射線治療的女性，後來在較年輕時發生乳癌的風險增加。
紐約市Sloan-Kettering癌症紀念中心小兒科成人長期追蹤計畫主任Kevin C. Oeffinger醫師表示，這個增加的風險在胸部放射線治療之後8年就可能會出現，且增加追蹤期間時，不會趨於平緩。
這些婦女在40-45歲時的乳癌累積發生率為13%至20%。
Oeffinger醫師與兒童腫瘤小組(COG)的研究同僚表示，這個差異和那些BRCA基因突變的婦女相似。
這篇發表於4月6日內科醫學誌(Annals of Internal Medicine)的回顧指出，這些婦女約有三分之二在一開始是治療何杰金氏淋巴瘤，她們的乳癌風險隨著早期胸部放射療法的劑量增加而增加。
COG報告指出，這些病患似乎可以從早期偵測中獲益，因此，當年輕時放射線劑量達20 Gy以上時，COG建議每年監測乳房攝影以及磁振造影(MRI)，在25歲時開始或者是完成放射線治療後8年開始，看哪個時間點比較慢。
不過，這個年度監測建議有一些需注意之處。
COG作者們在篩檢相關偽陽性方面寫道，有關可能傷害的瞭解太少，此外，額外的不必要的檢查和切片，情緒上的負擔以及經濟上的花費等等。
另外，這些婦女進行乳房攝影會接受更多放射線。
作者們寫道，另一個可能的傷害是，放射線引起乳癌的額外風險。
Oeffinger醫師向Medscape Oncology表示，標準的兩角度乳房攝影讓一名婦女曝露的放射劑量約為3.85 mGy。
作者們指出，在25歲開始接受監測的婦女，會比接受一般在40歲開始篩檢的婦女多出至少15次以上的乳房攝影。
不過，如同COG作者們指出，著眼於乳房攝影之「偵測誘發乳癌比率」的研究發現，或許無法應用到接受較高之治療性放射線劑量的婦女，簡而言之，此比率未知。
作者們提到未知的變數時表示，需要後續研究以更清楚定義終身監測的傷害與利益，包括乳房攝影相關放射線曝露的影響。
此外，因為COG建議這些婦女及早開始以乳房攝影和MRI進行監測，專家們對年度篩檢加以背書，他們寫道，有限的證據指出，特定監測對這個高風險族群有幫助。
【研究發現與介入之需要】
醫師要和這些婦女討論乳癌風險與監測時，首先須知道在孩童時、青春期與青少年時的胸部放射線癌症治療史。
作者們寫道，婦女自己也須知道，所以才需要介入。
Oeffinger醫師表示，在Sloan-Kettering癌症紀念中心，提供婦女的早期癌症治療和風險摘要，以及監測建議，我們提供病患一份一頁載有此資訊的摘要，並和他們討論，我們女性病患的監測率超過90%。
為了評估此一族群的乳癌風險，Oeffinger醫師與他的COG夥伴分析了11個回溯世代研究和3個案例控制研究，世代研究包括了超過14,000名婦女，其中7,000人在2000年前因為某種癌症接受了胸部放射線治療，有422個婦女後來發生乳癌。
在較高品質的世代研究中，每10,000人年的標準發生率範圍為13.3- 55.5，每10,000人年的絕對過度風險範圍為18.6-79.0。
案例控制研究之一發現，在15歲時接受何杰金氏淋巴瘤診斷的女性，以及在25歲接受建議進行篩檢者，到了45歲時，接受放射線劑量20 -39Gy者發生乳癌的機率為9.2%，接受放射線劑量40 Gy 以上者發生乳癌的機率為11.1%。
作者們觀察發現，相較於在青春期接受放射線者，孩童期接受胸部放射線治療癌症者沒有保護力。
他們寫道，如同一些早期研究所認為的，青春期之前治療的婦女其風險並沒有比那些在青春期治療者低，延長追蹤年數的研究也未發現青春期之前胸部放射線治療之婦女的乳癌風險和在青春期治療者有差異。
至於這些婦女的乳癌臨床特徵，以及診斷後的結果，作者們發現，現有的有限證據認為，她們和一般人口的女性相似。
國家癌症研究中心資助該研究。Oeffinger醫師宣告沒有相關財務關係。
Breast Cancer Surveillance Recommended When Chest Irradiated for Cancer Early in Life
By Nick Mulcahy
Medscape Medical News
April 6, 2010 — Women treated with chest radiation for cancer during childhood, adolescence, or young adulthood have a substantially elevated risk for breast cancer at a relatively young adult age, according to a new systematic review on the subject.
The increased risk is found as early as 8 years after chest radiation and does "not plateau with increasing length of follow-up," according to the review authors, led by Kevin C. Oeffinger, MD, director of the Adult Long-Term Follow-Up Program in the Departments of Pediatrics and Medicine at the Memorial Sloan-Kettering Cancer Center in New York City.
The cumulative incidence of breast cancer by 40 to 45 years in these women ranged from 13% to 20%.
This incidence is similar to that in women with a BRCA gene mutation.
"This incidence is similar to that in women with a BRCA gene mutation," write Dr. Oeffinger and his colleagues from the Children's Oncology Group (COG).
The review, which is published in the April?6 issue of the Annals of Internal Medicine, noted that about two thirds of these women were initially treated for Hodgkin's lymphoma. Their breast cancer risk increased linearly with the dose of the earlier chest radiation.
The COG reports that "there seems to be a benefit from early detection" in these patients. Thus, when there is radiation of 20?Gy or more early in life, the COG recommends annual surveillance mammography and magnetic resonance imaging (MRI) starting either at the age of 25 years or 8 years after completion of radiation therapy, whichever occurred last.
Nevertheless, this approach to annual surveillance is a recommendation with caveats.
"Too little is understood about the potential harms," write the COG authors about screening-related false-positives, additional unnecessary testing and biopsies, and the emotional and economic costs.
And there is also the matter of giving more radiation to these women via mammograms.
"Another potential harm is the additional risk for radiation-induced breast cancer," write the authors.
A standard 2-view mammogram exposes a woman to about 3.85?mGy.
"A standard 2-view mammogram exposes a woman to about 3.85?mGy," Dr. Oeffinger told Medscape Oncology.
Women who start receiving surveillance at the age of 25 would have at least 15 more mammographies than women who undergo usual screening, which begins at the age of 40, note the authors.
However, as the COG authors note, findings from researchers who have looked at the "detected-induced [breast cancer] ratio" from mammography are probably not applicable to the population of women treated with high doses of therapeutic radiation. In short, the ratio is unknown.
"Further research is required to better define the harms and benefits of lifelong surveillance," say the authors about the variety of unknowns, including the effects of mammography-related radiation exposure.
Still, given the COG recommendation for these women to start early surveillance with mammography and MRI, these experts endorse annual screening. "Limited evidence indicates that specialized surveillance will benefit this high-risk population," they write.
Study Findings and the Need to Intervene
Clinicians who want to discuss breast cancer risk and surveillance with these women first need to know the history of chest radiation for cancer during childhood, adolescence, and young adulthood.
The women need to know it too, write the study authors, so "interventions" are needed.
At Memorial Sloan-Kettering, women are provided with a summary of their earlier cancer treatment and risks, and a recommendation for surveillance, according to Dr. Oeffinger. "We give our patients a 1-page summary with this information and discuss it with them. The surveillance rate of our women exceeds 90%," he said.
To assess breast cancer risk in this population, Dr. Oeffinger and his COG colleagues looked at 11 retrospective cohort studies and 3 case–control studies. The cohort studies consisted of more than 14,000 women, 7,000 of whom received chest radiation for some kind of cancer before the year 2000. There were 422 women who subsequently developed breast cancer.
Among the "higher-quality" cohort studies, the standardized incidence ratio ranged from 13.3 to 55.5 per 10,000 person-years, and the absolute excess risk ranged from 18.6 to 79.0 per 10,000 person-years.
One of the case–control studies found that, among women who received a diagnosis of Hodgkin's lymphoma at the age of 15 and were counseled to undergo screening at the age of 25, 9.2% of those who received 20 to 39?Gy and 11.1% of those who received 40?Gy or more would develop breast cancer by the age 45.
Receiving radiation to the chest for cancer in childhood is not protective, compared with receiving radiation in adolescence, observe the authors.
"Risk in women treated before puberty is not lower than that in those treated during adolescence, as suggested by some early studies," they write. Studies with extended years of follow-up have not found a difference in breast cancer risk between women treated with chest radiation before puberty and those treated in adolescence, they note.
With regard to the clinical characteristics of breast cancer in these women and the outcomes after diagnosis, the authors found that "available limited evidence" suggests that they are similar to those of women in the general population."
The study was funded by the National Cancer Institute. Dr. Oeffinger has disclosed no relevant financial relationships.
Ann Intern Med. 2010;152:444-455.
