Researchers Oppose Unvalidated Gene Panel Tests for Cancer Links

“A group of international researchers is making the case that genetic tests that look for multiple hereditary genes suspected of being linked to breast cancer should not be offered until they are proven to be valid and useful in clinical practice.

“Such tests, made by several companies including Myriad Genetics Inc, Ambry Genetics, Invitae and Illumina Inc, cover up to 100 inherited cancer genes, including more than 20 for breast cancer.

“They have become increasingly popular since June 2013, when the U.S. Supreme Court invalidated patents held by Myriad on BRCA1 and BRCA2, two well-characterized genes that put a woman at high risk for breast, ovarian and other cancers.

“What the researchers are concerned about are lesser-known genes included in the tests.

” ‘The reality is that we don’t have good risk estimates for mutations that occur in many of the genes on the panels,’ said Fergus Couch, a breast cancer expert at Mayo Clinic in Rochester, Minnesota.”


New Genetic Tests for Breast Cancer Hold Promise

“A Silicon Valley start-up with some big-name backers is threatening to upend genetic screening for breast and ovarian cancer by offering a test on a sample of saliva that is so inexpensive that most women could get it.

“At the same time, the nation’s two largest clinical laboratories, Quest Diagnostics and LabCorp, normally bitter rivals, are joining with French researchers to pool their data to better interpret mutations in the two main breast cancer risk genes, known as BRCA1 and BRCA2. Other companies and laboratories are being invited to join the effort, called BRCA Share.

“The announcements being made on Tuesday, although coincidental in their timing, speak to the surge in competition in genetic risk screening for cancer since 2013, when the Supreme Court invalidated the gene patents that gave Myriad Genetics a monopoly on BRCA testing.

“The field has also been propelled by the actress and filmmaker Angelina Jolie, who has a BRCA1 mutation and has written about her own decision to have her breasts, ovaries and fallopian tubes removed to sharply reduce her risk of developing cancer.

“But the issue of who should be tested remains controversial. The effort of the start-up, Color Genomics, to ‘democratize access to genetic testing,’ in the words of the chief executive, Elad Gil, is generating concern among some experts.”


BRCA Mutation Testing in Triple Negative Breast Cancer Useful Even When There Is No Family History

The gist: Recent research shows that testing for BRCA1 and BRCA2 mutations might be useful for patients with triple-negative breast cancer, even if they have no family history of breast cancer.

“The high prevalence of deleterious mutations in predisposition genes in patients with triple-negative breast cancer unselected for family history suggests germline genetic testing for BRCA1 and BRCA2 mutations may be appropriate in this population, according to study results.

“However, further analyses of non-BRCA genes are needed to assess their utility in this setting, researchers wrote.

“Fergus J. Couch, PhD, of the department of laboratory medicine and pathology at Mayo Clinic in Rochester, Minn., and colleagues evaluated data from 1,824 women with triple-negative breast cancer who were enrolled on one of 12 studies. All women were unselected for family history of breast or ovarian cancer, and most were non-Hispanic white (97%). The median age of the population at diagnosis was 51 years (range, 22-93).”


MRI Improved Mammography Screening Sensitivity for Older BRCA Mutation Carriers

“The addition of MRI to mammography significantly improved screening sensitivity among women who harbored BRCA1 or BRCA2 mutations, according to study results.

“The sensitivity of the screening combination also was comparable among women aged older than 50 years and those aged younger than 50 years, results showed.

“Xuan-Anh Phi, PhD, of University Medical Center Groningen in the Netherlands, and colleagues pooled individual patient data from six screening trials of high-risk individuals.

“The trials comprised a combined 1,951 women with BRCA1/2 mutations. The median age of the entire population was 41 years; 16.9% were aged 50 to 59 years and 5.5% were aged 60 years or older.

“Of the breast cancers detected, 141 occurred in women aged younger than 50 years, and 43 occurred in women aged 50 years or older.

“MRI detected 78.8% of the cancers, and mammography detected 38.6%. The combination of MRI and mammography detected 88.6% of the cancers and was associated with a significant improvement in screening sensitivity compared with mammography alone (93.4% vs. 39.6%; P˂.001). However, the combination of both screening methods was associated with a reduced specificity compared with mammography alone (80.3% vs. 93.6%; P=.0016).”


Phone Support Groups Help Women with BRCA Mutations Cope with Stress

“In an Australian study reported in the Journal of Clinical Oncology, White et al found that a telephone-based peer-support intervention reduced breast cancer distress among women with a BRCA1 or BRCA2 gene mutation.

“In the study, 207 mutation carriers reporting interest in talking to other mutation carriers were randomly assigned to the peer-support intervention (n = 105) or usual care (n = 102). The intervention involved trained peer volunteers’ contacting study participants six times over 4 months to provide informational, emotional, and practical support. Outcomes included breast cancer distress (measured by Impact of Event Scale), anxiousness, unmet information needs, and stress and confidence (measured by Cognitive Appraisals About Genetic Testing scale). Outcomes were assessed at the end of intervention (4 months after randomization) and 2 months later…

“The investigators concluded: ‘The intervention is effective in reducing distress and unmet information needs for this group of women. Identifying strategies for prolonging intervention effects is warranted.’ ”


Common Chemotherapy Is Not Heart Toxic in Patients with BRCA1/2 Mutations

“Use of anthracycline-based chemotherapy, a common treatment for breast cancer, has negligible cardiac toxicity in women whose tumors have BRCA1/2 mutations—despite preclinical evidence that such treatment can damage the heart.

“The findings, to be presented at the 2014 San Antonio Breast Cancer Symposium (SABCS), represent a unique effort between cardiologists and oncologists at Georgetown Lombardi Comprehensive Cancer Center and MedStar Heart & Vascular Institute in Washington to answer a vital clinical question.

” ‘Our study was prompted by evidence from animal studies suggesting that mice with BRCA1/2 mutations in the heart were susceptible to heart damage—treatment with anthracyclines led to reduced cardiac function and heart failure much more frequently in these mice than in those without these mutations,’ says the study’s principal investigator, Ana Barac, MD, PhD, an assistant professor of medicine at Georgetown University School of Medicine and director of the cardio-oncology program at MedStar Heart & Vascular Institute.”


Triple-Negative Breast Cancer Patients Should Undergo Genetic Screening

“Most patients with triple-negative breast cancer should undergo genetic testing for mutations in known breast cancer predisposition genes, including BRCA1 and BRCA2, a Mayo Clinic-led study has found. The findings come from the largest analysis to date of genetic mutations in this aggressive form of breast cancer. The results of the research appear in the Journal of Clinical Oncology.

” ‘Clinicians need to think hard about screening all their triple-negative patients for mutations because there is a lot of value in learning that information, both in terms of the risk of recurrence to the individual and the risk to family members. In addition, there may be very specific therapeutic benefits of knowing if you have a mutation in a particular gene,’ says Fergus Couch, Ph.D., professor of laboratory medicine and pathology at Mayo Clinic and lead author of the study.

“The study found that almost 15 percent of triple-negative breast cancer patients had deleterious (harmful) mutations in predisposition genes. The vast majority of these mutations appeared in genes involved in the repair of DNA damage, suggesting that the origins of triple-negative breast cancer may be different from other forms of the disease. The study also provides evidence in support of the National Comprehensive Cancer Network (NCCN) guidelines for genetic testing of triple-negative breast cancer patients.

“Triple-negative breast cancer is a specific subset of breast cancer that makes up about 12 to 15 percent of all cases. The disease is difficult to treat because the tumors are missing the estrogen, progesterone and HER-2 receptors that are the target of the most common and most effective forms of therapy. However, recent studies have suggested that triple-negative breast cancer patients might harbor genetic mutations that make them more likely to respond to alternative treatments like cisplatin, a chemotherapy agent, or PARP inhibitors, anti-cancer agents that inhibit the poly (ADP-ribose) polymerase (PARP) family of enzymes.”


'Screen More' for Cancer Risk Genes

“Mutations in BRCA genes can give women up to an 80% chance of developing breast cancer.

“A trial involving 1,034 Ashkenazi Jews, who are at high risk, suggested more than half of their cases were not being picked up under the current NHS guidelines.

“The Eve Appeal charity said wider testing would save lives and money.

“Mutations in BRCA genes stop DNA repairing itself and increase the risk of cancer developing.

“As well as breast cancer, they are also linked to ovarian and prostate cancers.”


With Gene Mutations, Second Breast Cancer Risk Rises over Time

“Women who are genetically susceptible to breast cancer and develop it in one breast are at higher than average risk for a tumor in the other breast, and that risk may increase as time goes on, according to a new analysis.

“Mutations in the BRCA 1 or 2 genes increase the risk for several types of cancer and account for 5 percent to 10 percent of breast cancers, according to the National Cancer Institute.

“Researchers from Spain reviewed 20 studies of the risk of cancer in the second breast of BRCA 1 and 2 carriers.

“For breast cancer patients with the BRCA 1 mutation, the risk of a cancer in the opposite breast rose from 15 percent at five years after diagnosis to 27 percent at 10 years and 33 percent at 15 years.

“For the BRCA 2 mutation, the risk increased from nine percent at five years to 19 percent at 10 years to 23 percent at 15 years.

“For women with neither mutation, the risk of cancer in the opposite breast stayed low at 3 percent and 5 percent at the five and 10 year marks, according to results in the journal The Breast. There wasn’t enough data to estimate the 15-year risk in this group, the authors write.”