Most patients with cancer are not undergoing germline genetic testing

IF 503.1 1区 医学 Q1 ONCOLOGY CA: A Cancer Journal for Clinicians Pub Date : 2024-01-19 DOI:10.3322/caac.21827
Mike Fillon
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The study appears in the <i>Journal of the American Medical Association</i> (doi:10.1001/jama.2023.9526).</p><p>For the study, researchers included patients from California and Georgia in the Surveillance, Epidemiology, and End Results (SEER) registries, who were at least age 20 years, and diagnosed with any cancer between January 1, 2013, and March 31, 2019. Genes were grouped by cancer types and recommended for testing according to the National Comprehensive Cancer Network’s practice guidelines. Four laboratories submitted gene-level interpretations while also checking nationwide for patients who may have moved to other states.</p><p>There were 1,369,602 patients selected for the study. Patient variables included sex, cancer stage at diagnosis, age at diagnosis, ethnicity, and race. They also included companion genetic testing resulted comprising 107 genes of interest. The results were classified as pathogenic, benign, or uncertain.</p><p>The patients who underwent testing varied by the following cancer types: 50% had male breast cancer, 38.6% had ovarian cancer, 26% had female breast cancer, 7.5 had more than one cancer type, 6.4% had endometrial cancer, 5.6% had pancreatic cancer, 5.6% had colorectal cancer, 1.1% had prostate cancer, and 0.3% had lung cancer.</p><p>The researchers also found that testing overall increased during the time of the study. Of particular note, they found that testing in patients with pancreatic cancer increased from 1.2% in 2013 to 18.6% in 2019. This increase was not even, however; testing for patients with lung cancer remained low, increasing only from 0.1% in 2013 to 0.8% in 2019. They also found lower rates of genetic testing in older patients; although 18% of patients age 40 years were tested, only 2% of patients at age 80 years were tested.</p><p>The study authors noted that of all the pathogenic results, 67.5% to 94.9% of gene variants were in those genes that practice guidelines recommend testing. They also found that 68.3% to 83.8% of variants identified were in genes that have been linked to cancer type. “Gastrointestinal cancer–associated genes represented 68.3% of pathogenic results in colorectal cancer and 71.8% of pathogenic results in endometrial cancer,” they wrote. “Breast and ovarian cancer–associated genes represented 79.5% of pathogenic results in female breast cancer, 83.8% in male breast cancer, and 82.0% in ovarian cancer.” In addition, they remarked that non–guideline recommended genes represented between 5.1% of pathogenic results in endometrial cancer and 28.1% of pathogenic results in pancreatic cancer.</p><p>Lead study author, Allison W. Kurian, MD, MSc, professor of medicine, epidemiology and population health at Stanford University School of Medicine in Stanford, California, says that this study breaks new ground by telling us how a major development in cancer prevention and treatment—genetic testing—can benefit patient care at the population level. “Before this study, we had little idea of whether evidence-based practice guidelines for genetic testing after a cancer diagnosis—for example, that all patients with male breast, ovarian, or pancreatic cancer should receive genetic testing—were being met.</p><p>“We also knew little about racial and ethnic disparities in genetic testing, or about genetic testing results among people with cancer in the general United States population,” she adds. “In this study, we addressed these knowledge gaps by linking the population-based cancer registries of Georgia and California to genetic testing records from the laboratories that provide nearly all such testing.”</p><p>Breast oncologist and clinical geneticist Mark E. Robson, MD, at Memorial Sloan Kettering Cancer Center in New York, New York, says that the study is important because it is a well-done population-based study that confirms smaller studies indicating that testing for cancer susceptibility is underused, and that there are significant disparities in who gets tested. “This is unfortunate since testing for cancer susceptibility is often very important for prevention of second cancers as well as for planning screening strategies for family members.”</p><p>Dr Robson says that the under-penetration of genetic testing is something that has been ongoing for many years, despite acceptance of its potential importance not only for risk stratification, but increasingly for treatment. “Awareness among clinicians is one challenge, but other barriers may be more important. 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引用次数: 0

Abstract

Science editor Amy H from Santa Clarita, California, was aware of her immediate family’s heavy cancer history so it came as no surprise to her when she was diagnosed with cancer—a stage 1 tumor in the transverse colon. However, nagging questions remained: Did lifestyle, environment, or other factors play a role in her diagnosis, or could her cancer possibly have been tied to a genetic history?

A new study has found that her uncertainty and anxiety are not uncommon: Most patients with cancer do not undergo germline testing to learn if their cancer may have been associated with an inherited gene mutation. The study appears in the Journal of the American Medical Association (doi:10.1001/jama.2023.9526).

For the study, researchers included patients from California and Georgia in the Surveillance, Epidemiology, and End Results (SEER) registries, who were at least age 20 years, and diagnosed with any cancer between January 1, 2013, and March 31, 2019. Genes were grouped by cancer types and recommended for testing according to the National Comprehensive Cancer Network’s practice guidelines. Four laboratories submitted gene-level interpretations while also checking nationwide for patients who may have moved to other states.

There were 1,369,602 patients selected for the study. Patient variables included sex, cancer stage at diagnosis, age at diagnosis, ethnicity, and race. They also included companion genetic testing resulted comprising 107 genes of interest. The results were classified as pathogenic, benign, or uncertain.

The patients who underwent testing varied by the following cancer types: 50% had male breast cancer, 38.6% had ovarian cancer, 26% had female breast cancer, 7.5 had more than one cancer type, 6.4% had endometrial cancer, 5.6% had pancreatic cancer, 5.6% had colorectal cancer, 1.1% had prostate cancer, and 0.3% had lung cancer.

The researchers also found that testing overall increased during the time of the study. Of particular note, they found that testing in patients with pancreatic cancer increased from 1.2% in 2013 to 18.6% in 2019. This increase was not even, however; testing for patients with lung cancer remained low, increasing only from 0.1% in 2013 to 0.8% in 2019. They also found lower rates of genetic testing in older patients; although 18% of patients age 40 years were tested, only 2% of patients at age 80 years were tested.

The study authors noted that of all the pathogenic results, 67.5% to 94.9% of gene variants were in those genes that practice guidelines recommend testing. They also found that 68.3% to 83.8% of variants identified were in genes that have been linked to cancer type. “Gastrointestinal cancer–associated genes represented 68.3% of pathogenic results in colorectal cancer and 71.8% of pathogenic results in endometrial cancer,” they wrote. “Breast and ovarian cancer–associated genes represented 79.5% of pathogenic results in female breast cancer, 83.8% in male breast cancer, and 82.0% in ovarian cancer.” In addition, they remarked that non–guideline recommended genes represented between 5.1% of pathogenic results in endometrial cancer and 28.1% of pathogenic results in pancreatic cancer.

Lead study author, Allison W. Kurian, MD, MSc, professor of medicine, epidemiology and population health at Stanford University School of Medicine in Stanford, California, says that this study breaks new ground by telling us how a major development in cancer prevention and treatment—genetic testing—can benefit patient care at the population level. “Before this study, we had little idea of whether evidence-based practice guidelines for genetic testing after a cancer diagnosis—for example, that all patients with male breast, ovarian, or pancreatic cancer should receive genetic testing—were being met.

“We also knew little about racial and ethnic disparities in genetic testing, or about genetic testing results among people with cancer in the general United States population,” she adds. “In this study, we addressed these knowledge gaps by linking the population-based cancer registries of Georgia and California to genetic testing records from the laboratories that provide nearly all such testing.”

Breast oncologist and clinical geneticist Mark E. Robson, MD, at Memorial Sloan Kettering Cancer Center in New York, New York, says that the study is important because it is a well-done population-based study that confirms smaller studies indicating that testing for cancer susceptibility is underused, and that there are significant disparities in who gets tested. “This is unfortunate since testing for cancer susceptibility is often very important for prevention of second cancers as well as for planning screening strategies for family members.”

Dr Robson says that the under-penetration of genetic testing is something that has been ongoing for many years, despite acceptance of its potential importance not only for risk stratification, but increasingly for treatment. “Awareness among clinicians is one challenge, but other barriers may be more important. Such barriers include the lack of time available for providers to educate patients about the possible benefits of testing, ongoing misunderstandings about risks, and outdated testing protocols that mandate assessment by cancer genetics specialists before testing. These barriers are particularly problematic for under-represented minorities and deep rural populations who have more limited access. The message is that clinicians should redouble their efforts to identify and test those who are at risk for carrying a genetic alteration that increases the risk of cancer.”

Dr Kurian agrees that genetic testing is tremendously under-utilized, with far fewer people being tested after a cancer diagnosis than the guidelines recommend. She says she cannot stress enough the significant racial and ethnic disparities in genetic testing, with Black/African American patients being the least likely to receive genetic testing and, consequently, the most likely to receive inconclusive genetic testing results. “These deficits are important targets for intervention.”

For Amy H, her mystery was solved when, at the recommendation of her oncologist, she underwent genetic testing and was diagnosed with Lynch syndrome. “I’d never even heard of Lynch syndrome before, and with both of my parents and all my grandparents gone, my relatives are few and far between,” she says. “The fact that it was colon cancer was a bit of a surprise, as, to my knowledge, no one in my family has a history of that particular type of cancer. The Lynch syndrome, though, was even more of a surprise.”

Amy H believes her history exemplifies the need for genetic testing even after a cancer diagnosis. “I believe it’s vital for those who’ve had a cancer diagnosis to receive genetic testing to help reduce risk of further incidences of cancer,” she says. “No one in my family had colon cancer, which is a prominent risk of Lynch syndrome. I have a colonoscopy every year now, and polyps have been found each time. Without the genetic testing, I wouldn’t know, and I’d run the risk of getting cancer again instead of preventing it in the first place.”

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大多数癌症患者都没有接受种系基因检测。
"临床医生的认识是一项挑战,但其他障碍可能更为重要。这些障碍包括:医疗服务提供者没有时间向患者宣传检测可能带来的益处;对风险的误解一直存在;过时的检测方案规定检测前必须由癌症遗传学专家进行评估。这些障碍对于代表性不足的少数族裔和偏远农村地区的人群来说尤为棘手,因为他们的就医渠道更为有限。库里安博士也认为基因检测的利用率极低,癌症诊断后接受检测的人数远远少于指南建议的人数。她说,基因检测在种族和人种方面存在显著差异,黑人/非洲裔美国人患者最不可能接受基因检测,因此也最有可能得到不确定的基因检测结果,这一点她怎么强调都不为过。"这些缺陷是干预的重要目标。"对于艾米-H来说,当她在肿瘤学家的建议下接受基因检测并被确诊为林奇综合征时,她的谜团被解开了。"她说:"我以前从未听说过林奇综合征,而且我的父母和祖父母都已去世,我的亲戚很少。她说:"结肠癌的事实让我有点吃惊,因为据我所知,我的家族中没有人有这种特殊类型的癌症病史。不过,林奇综合征就更令人吃惊了。"艾米-H 认为,她的病史说明,即使在癌症确诊后,也有必要进行基因检测。"她说:"我认为,对于那些已经确诊癌症的人来说,接受基因检测以帮助降低再次患癌的风险是至关重要的。"我的家族中没有人得过结肠癌,而结肠癌是林奇综合征的一个主要风险。我现在每年都做结肠镜检查,每次都能发现息肉。如果没有基因检测,我就不会知道,我就有可能再次患上癌症,而不是从一开始就预防癌症。
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来源期刊
CiteScore
873.20
自引率
0.10%
发文量
51
审稿时长
1 months
期刊介绍: CA: A Cancer Journal for Clinicians" has been published by the American Cancer Society since 1950, making it one of the oldest peer-reviewed journals in oncology. It maintains the highest impact factor among all ISI-ranked journals. The journal effectively reaches a broad and diverse audience of health professionals, offering a unique platform to disseminate information on cancer prevention, early detection, various treatment modalities, palliative care, advocacy matters, quality-of-life topics, and more. As the premier journal of the American Cancer Society, it publishes mission-driven content that significantly influences patient care.
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