NEW YORK – New data highlighted this week at the San Antonio Breast Cancer Symposium has added evidence supporting the value of using polygenic risk scores (PRS) in assessing women's risk of developing breast cancer and confirmed that, when used in the clinic, PRS tests do lead to changes in patient screening.

纽约——本周在圣安东尼奥乳腺癌研讨会上强调的新数据增加了证据，支持使用多基因风险评分（PRS）评估女性患乳腺癌风险的价值，并证实，当在临床上使用PRS测试时，确实会导致患者筛查的变化。

PRS scores also, according to data presented at the meeting, can refine cancer risk in individuals with benign breast disease..

根据会议上提供的数据，PRS评分还可以改善良性乳腺疾病患者的癌症风险。。

While the breast cancer prevention community seems to be well sold on the notion that PRS can improve upon risk predictions, compared to clinical risk factors alone, studies of the impact this may have on patients' eventual outcomes are still pending.

虽然乳腺癌预防界似乎很看好PRS可以改善风险预测的观点，但与单独的临床风险因素相比，这可能对患者最终结局产生的影响的研究仍在等待中。

To try to fill that gap, Myriad Genetics, which markets a combined test that includes both hereditary cancer mutation testing and PRS, conducted a study examining the impact of what it calls a combined risk score (CRS) — a score that couples its approximately 150-gene PRS with the Tyrer-Cuzick risk calculator, which factors in age, family history, and other clinical factors — on the rate of certain interventions.

为了填补这一空白，Myriad Genetics进行了一项研究，研究了所谓的综合风险评分（CRS）对某些干预率的影响，该评分将其大约150个基因的PRS与Tyrer Cuzick风险计算器相结合，该计算器考虑了年龄，家族史和其他临床因素。

These include earlier mammography initiation and MRI imaging..

这些包括早期的乳房X光检查和MRI成像。。

Guidelines generally recommend more intense screening for individuals who have a 20 percent or more increase in cancer risk, said Katie Johansen Taylor, Myriad's VP of clinical product research and partnerships, who presented the results at the meeting on Wednesday.

Myriad临床产品研究与合作副总裁凯蒂·约翰森·泰勒（KatieJohansenTaylor）在周三的会议上介绍了研究结果，她说，指南通常建议对癌症风险增加20%或更多的个体进行更深入的筛查。

PRS testing is not specifically recommended by the National Comprehensive Cancer Network as a tool to guide clinical care, but Myriad wanted to explore whether patients who do get a high-risk result with its test see the same increase in interventions as individuals who only read as high risk by the Tyrer-Cuzick algorithm..

国家综合癌症网络并未特别推荐PRS测试作为指导临床护理的工具，但Myriad希望探索通过其测试获得高风险结果的患者是否会看到与仅通过Tyrer-Cuzick算法读取为高风险的个体相同的干预增加。。

The study used healthcare claims data from OptumLabs Data Warehouse for a total of 8,600 patients ages 18 or older, excluding those with past history of breast cancer and other potentially confounding historical health events.

这项研究使用了OptumLabs数据仓库中的医疗保健索赔数据，共有8600名18岁或以上的患者，不包括那些有乳腺癌病史和其他可能混淆历史健康事件的患者。

Investigators divided the cohort into four subgroups based on predicted lifetime risk of breast cancer by either the Myriad CRS or Tyrer-Cuzick alone. The first group included all patients who were considered high risk by both measures. The second had average risk by both measures, and the final two had discrepant results, with one test indicating high risk and the other average risk..

研究人员根据Myriad CRS或Tyrer Cuzick单独预测的乳腺癌终生风险，将队列分为四个亚组。第一组包括所有两种措施都被认为是高风险的患者。第二个指标的风险均为平均风险，最后两个指标的结果不一致，一个测试显示高风险，另一个测试显示平均风险。。

About half the cohort had dual average risk, a little more than a quarter had dual high-risk results. The rest, about 18 percent, had conflicting results.

大约一半的队列具有双重平均风险，略多于四分之一的队列具有双重高风险结果。其余约18%的人的结果相互矛盾。

Investigators reported that among the CRS-high risk cases, Tyrer-Cuzick called about 26 percent of cases as average risk. Meanwhile, for Tyrer-Cuzick-high risk patients, only about 13 percent had an average-risk CRS result.

调查人员报告说，在CRS高危病例中，TyrerCuzick称约26%的病例为平均风险。同时，对于TyrerCuzick高危患者，只有约13%的患者有平均风险CRS结果。

Cases with dual high-risk results had a significant increase in MRI screening, compared to the two subgroups with conflicting results. Screening mammography, though, didn't vary significantly across the groups, nor did the use of genetic counseling.

与结果相互矛盾的两个亚组相比，具有双重高风险结果的病例在MRI筛查中显着增加。然而，筛查乳房X光检查在各组之间没有显着差异，遗传咨询的使用也没有显着差异。

An audience member expressed surprise that the rate of MRI was so much higher for patients with high-risk CRS and Tyrer-Cuzick results when the guidelines don't directly recommend intensified screening based on PRS.

。

Taylor said that one of the goals of the study was to try to see if clinicians are taking PRS results seriously and acting upon them, as clinical demand can be one factor in influencing future guidelines.

泰勒说，这项研究的目标之一是试图看看临床医生是否认真对待PRS结果并采取行动，因为临床需求可能是影响未来指南的一个因素。

The current study did not look at cancer incidence and patient outcomes, but that could be something that the company could use claims data to help examine, Taylor said.

泰勒说，目前的研究没有考虑癌症发病率和患者预后，但这可能是该公司可以使用索赔数据来帮助检查的事情。

It's difficult to try to correlate test results with clinical outcomes, she added. 'We might be waiting decades for a person with a high risk of breast cancer to actually develop breast cancer so we need to come up with some creative ways to measure and power that study,' she said.

她补充道，很难将检测结果与临床结果联系起来她说：“我们可能要等几十年，才能让一个乳腺癌高危人群真正患上乳腺癌，因此我们需要想出一些创造性的方法来衡量和推动这项研究。”。

Alongside exploring clinical impact, Myriad is also working to validate an updated version of its test targeting a larger panel of both cancer-risk and ancestry-related variants.

除了探索临床影响外，Myriad还致力于验证其针对更大范围的癌症风险和祖先相关变异的测试的更新版本。

The test's performance across populations is a feature the company strongly emphasizes, and it was the focus of another presentation, on Thursday that reported results from a validation study of the CRS using the UK Biobank.

该测试在人群中的表现是该公司强烈强调的一个特征，也是周四另一场演讲的重点，该演讲报告了使用英国生物库对CRS进行验证研究的结果。

Myriad's UK Biobank study featured an updated version of its assay, which the company expanded to include 59 ancestry markers and about 300 breast cancer risk SNPs. The cohort included 200,000 women, a small subset of whom — about 12,000 — were non-White. Investigators compared CRS results to breast cancer incidence at a median of 11 months follow-up..

Myriad的英国生物库研究提供了其检测方法的更新版本，该公司将其扩展到包括59个祖先标记和约300个乳腺癌风险SNP。该队列包括200000名女性，其中一小部分（约12000名）是非白人。研究人员将CRS结果与中位随访11个月的乳腺癌发病率进行了比较。。

Comparing CRS testing with the use of Tyrer-Cuzick clinical risk assessment alone, the team saw that CRS did appear to outperform standalone risk testing. The calls Myriad's test made that Tyrer-Cuzick missed did show an increased incidence of breast cancer.

将CRS测试与单独使用Tyrer Cuzick临床风险评估进行比较，该团队发现CRS确实优于单独的风险测试。Myriad的测试显示，TyrerCuzick错过的电话确实显示乳腺癌发病率增加。

Fergus Couch, a researcher at the Mayo Clinic, called the test's performance stability across the White and non-White groups 'really nice.'

梅奥诊所的研究员费格斯·考奇（FergusCouch）称，测试在白人和非白人群体中的表现稳定性“非常好”

In a separate study, Mayo Clinic researchers also sought to demonstrate whether there is added value in using PRS to assess risk in patients with benign breast disease. This study was also an effort to replicate results from a prior collaborative study that showed that a PRS score consisting of 261 genes could identify patients with benign findings that were at a higher versus lower risk of developing malignancy..

在另一项研究中，梅奥诊所的研究人员还试图证明使用PRS评估良性乳腺疾病患者的风险是否具有附加价值。这项研究也是为了复制先前合作研究的结果，该研究表明，由261个基因组成的PRS评分可以识别出良性发现的患者，这些患者发生恶性肿瘤的风险较高而较低。。

Investigators tested banked samples from almost 4,000 women with either non-proliferative, proliferative without atypia, or atypical hyperplasia.

研究人员测试了近4000名非增殖性，无非典型增生性或非典型增生性女性的库存样本。

'Think of these as progressions events as you go along through the spectrum of benign breast disease,' said Couch. The study compared cases — those who later developed breast cancer — with controls who did not.

“当你经历良性乳腺疾病的范围时，可以将这些视为进展事件，”Couch说。该研究将后来患乳腺癌的病例与未患乳腺癌的对照组进行了比较。

In each of the three subgroups, PRS was higher in those who developed cancer. Surprisingly, there was no significant difference between the three subtypes.

在这三个亚组中，患有癌症的人的PRS均较高。令人惊讶的是，这三种亚型之间没有显着差异。

'That was a little unexpected,' Couch said. 'We would have thought maybe that the non-proliferative group, which is a very, very early form of benign breast disease, would not necessarily have read out that way.'

“这有点出乎意料，”考奇说我们可能会认为，非增殖性乳腺疾病是一种非常、非常早期的良性乳腺疾病，不一定会这样读出来。”

Overall, he said, the data indicate that PRS can be combined with the obvious risk factor of having benign breast disease to better measure risk.

他说，总体而言，数据表明PRS可以与患有良性乳腺疾病的明显风险因素相结合，以更好地衡量风险。

Couch said that while Myriad has been making strides in providing clinical PRS testing for breast cancer in the US, other countries are only now starting to embrace this type of approach.

Couch说，虽然Myriad在美国为乳腺癌提供临床PRS检测方面取得了长足进步，但其他国家现在才开始接受这种方法。

'We're seeing it start to take hold, but there's still a number of implementation studies that are being done around the world … that are still trying to show the clinical efficacy,' he said.

。