美國衛院大型研究 〔國際新聞中心／綜合報導〕美國國家衛生研究院領導的大型研究顯示，乳癌其實可根據基因類型不同細分為四種，而且這四種乳癌中，也發現有其他癌症的基因標記，換言之，其他癌症藥物或許也能用於治療乳癌。 歷來對乳癌最廣泛的基因分析 這是歷來針對乳癌最廣泛的基因分析，重新塑造了我們對乳癌的了解，也可望為乳癌療法開啟新道路；但研究團隊表示，目前還需要更廣泛的臨床研究才能證實相關成果，因此可能還要數年時間，此份研究成果才能真正應用在乳癌治療上。 這份研究觀察最常見的、乳腺管引起的乳癌，著重觀察尚未擴散到身體其他部位的初期乳癌，藉此判定可攻擊的基因改變，以在癌細胞轉移前加以阻止。研究辨識出至少四十種藥物可攻擊的基因變異，而其中多數是已有藥物可供治療、其他癌症的基因變異。 研究最驚人的發現，就是找到腫瘤細胞與皮膚以及汗腺基底癌細胞類似的乳癌。這種乳癌罹患率最低，與其他乳癌也截然不同，反而比較像是卵巢癌與一種肺癌。 也就是說，未來這種乳癌或許能以卵巢癌用藥、例如新型的ＰＡＲＰ抑制劑來治療。 第二與第三種乳癌最常見，其表面有蛋白質，會攫取雌激素，加速癌細胞成長。由於此種乳癌產生自乳腺的管細胞，因此稱為管狀Ａ型與管狀Ｂ型乳癌。管狀Ａ型預後佳，管狀Ｂ型則否，因此管狀Ａ型乳癌或許能以荷爾蒙療法，來抑制雌激素刺激癌細胞生長，管狀Ｂ型乳癌則需化療。 第四種癌症稱為HER2陽性乳癌，這類乳癌患者通常擁有兩對HER2基因，一種稱為賀癌平（Herceptin）的藥物可阻止這種基因，並改變病患預後。 這份二十三日刊登於「自然」期刊的研究，是分析八百二十五名乳癌病患的腫瘤後得出的成果。此份研究是大型聯邦計畫癌症基因組地圖（Cancer Genome Atlas）的一部分，同一計畫內針對肺癌與大腸癌的基因分析最近也已公布。美研究︰乳癌分四種 發現基因標記
Genetic Study Divides Breast Cancer Into 4 Distinct Types
By GINA KOLATA
NYT 2012-9-23
In findings that are fundamentally reshaping the scientific understanding of breast cancer, researchers have identified four genetically distinct types of the cancer. And within those types, they found hallmark genetic changes that are driving many cancers.
These discoveries are expected to lead to new treatments with drugs already approved for cancers in other parts of the body and new ideas for more precise treatments aimed at genetic aberrations that now have no known treatment.
The study, published online on Sunday in the journal Nature, is the first comprehensive genetic analysis of breast cancer, which kills more than 35,000 women a year in the United States. The new paper, and several smaller recent studies, are electrifying the field.
“This is the road map for how we might cure breast cancer in the future,” said Dr. Matthew Ellis of Washington University, a researcher for the study.
Researchers and patient advocates caution that it will still take years to translate the new insights into transformative new treatments. Even within the four major types of breast cancer, individual tumors appear to be driven by their own sets of genetic changes. A wide variety of drugs will most likely need to be developed to tailor medicines to individual tumors.
“There are a lot of steps that turn basic science into clinically meaningful results,” said Karuna Jaggar, executive director of Breast Cancer Action, an advocacy group. “It is the ‘stay tuned’ story.”
The study is part of a large federal project, the Cancer Genome Atlas, to build maps of genetic changes in common cancers. Reports on similar studies of lung and colon cancer have been published recently. The breast cancer study was based on an analysis of tumors from 825 patients.
“There has never been a breast cancer genomics project on this scale,” said the atlas’s program director, Brad Ozenberger of the National Institutes of Health.
The investigators identified at least 40 genetic alterations that might be attacked by drugs. Many of them are already being developed for other types of cancer that have the same mutations. “We now have a good view of what goes wrong in breast cancer,” said Joe Gray, a genetic expert at Oregon Health & Science University, who was not involved in the study. “We haven’t had that before.”
The study focused on the most common types of breast cancer that are thought to arise in the milk duct. It concentrated on early breast cancers that had not yet spread to other parts of the body in order to find genetic changes that could be attacked, stopping a cancer before it metastasized.
The study’s biggest surprise involved a particularly deadly breast cancer whose tumor cells resemble basal cells of the skin and sweat glands, which are present in the deepest layer of the skin. These breast basal cells form a scaffolding for milk duct cells. Such cancers are often called triple negative but the study researchers call them basal-like.
Basal-like cancers are most frequent in younger women, in African-Americans and in women with breast cancer genes BRCA1 and BRCA2.
And, the researchers report, their genetic derangements make these cancers a much closer kin of ovarian cancers than of other breast cancers. Basal-like breast cancers also resemble squamous cell cancer of the lung.
“It’s incredible,” said Dr. James Ingle of the Mayo Clinic, one of the study’s 348 authors, of the ovarian cancer connection. “It raises the possibility that there may be a common cause.”
The study gives a biologic reason to try routine treatments for ovarian cancer — platinum drugs, for example — in basal-like breast cancer, the investigators said. And a common class of drug used in breast cancer, anthracyclines (adriamycin or epirubicin), might be dropped from the basal-like cancer treatment regimen because they do not increase help in ovarian cancer.
Anthracyclines, Dr. Ellis said, “are the drugs most breast cancer patients dread because they are associated with heart damage and leukemia.”
A new type of drug, PARP inhibitors, that seems to help squelch ovarian cancers, should also be tried in basal-like breast cancer, Dr. Ellis said.
Two other types of breast cancer, accounting for most cases of the disease, arise from the luminal cells that line milk ducts. These cancers have proteins on their surfaces that grab estrogen, fueling their growth. Just about everyone with estrogen-fueled cancer gets the same treatment. Some do well. Others do not.
The genetic analysis divided luminal cancers into two distinct subtypes. The luminal A subtype had good prognoses while luminal B did not, suggesting that perhaps patients with luminal A tumors might do well with just hormonal therapy to block estrogen from spurring their cancers while luminal B patients might do better with chemotherapy in addition to hormonal therapy.
In some cases, genetic aberrations were so strongly associated with one or the other luminal subtype that they appeared to be the actual cause of the cancer, said Dr. Charles Perou of the University of North Carolina, who is the lead author of the study. And he called that “a stunning finding.”
“We are really getting at the roots of these cancers,” he said.
After basal-like cancers, and luminal A and B cancers, the fourth type of breast cancer is what the researchers called HER2-enriched. Breast cancers often have extra copies of a gene, HER2, that drives their growth. A drug, Herceptin, can block the gene and has changed the prognosis for these patients from one of the worst in breast cancer to one of the best.
Yet although Herceptin is approved for every breast cancer patient whose tumor makes too much HER2, the new analysis finds that not all of these tumors are alike. The HER2-enriched should respond readily to Herceptin; the other type might not.
The only way to know is to do a clinical trial, and one is already being planned. Herceptin is expensive and can occasionally damage the heart. “We absolutely only want to give it to patients who can benefit,” Dr. Perou said.
For now, despite the tantalizing possibilities, patients will have to wait for clinical trials to see whether drugs that block the genetic aberrations can stop the cancers. And it could be a massive undertaking to get all the drug testing done. Because there are so many different ways a breast cancer cell can go awry, there may have to be dozens of drug studies, each focusing on a different genetic change.
One of Dr. Ellis’s patients, Elizabeth Stark, 48, has a basal-type breast cancer. She has gone through three rounds of chemotherapy, surgery and radiation over the past four years. Her disease is stable now and Dr. Stark, a biochemist at Pfizer, says she knows it will take time for the explosion of genetic data to produce new treatments that might help her.
“In 10 years it will be different,” she said, adding emphatically, “I know I will be here in 10 years.”
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