A Q&A with Rama Gullapalli, MD, PhD; a a physician-scientist in the departments of Pathology, Chemical and Biological Engineering at the University of New Mexico. His research lab focuses on the role of the environment in hepatobiliary cancers. He is also a practicing molecular pathologist with an interest in emerging molecular diagnostics, next generation sequencing and bioinformatics. Email: firstname.lastname@example.org
Q: A recent New York Times op-ed piece from an NYU Langone Health professor urged an aggressive approach to screening for early-stage pancreatic cancer. Despite optimism, the history of cancer screening is rife with trouble, the harms often exceeding the benefits. What do you think is the best way to proceed?
A: Imagine a scenario.
A new cancer test hits the market with some impressive characteristics: a detection sensitivity of 95% and a specificity of an equally impressive 95%. If you were asked the question, “Given a positive test result, what are your chances of actually having cancer?” and you guessed a number of 80 or 90%, you would not be alone. But you’d be wrong.
The key missing information necessary to answer this question is the disease probability among the general population. The number of new cases of cancer detected every year in the U.S. is about 462 cases per 100,000 people. This means that the probability of a new cancer being detected in a member of the U.S. population annually is roughly 0.00462%. Incorporating this information leads to only an 8.1% chance of having cancer for a test that is positive! This is what is called an inverse probability problem. Continue reading…
“Only 1 treatment option is currently available for treating patients with metastatic germline BRCA-mutated triple-negative breast cancer (TNBC), but research into novel therapies, including PI3K/conjugates (ADCs) could soon result in a host of new therapies for this hard-to-treat disease.
” ‘Right now, for TNBC, chemotherapy is our only option,’ said Joyce A. O’Shaughnessy, MD, co-chair of Breast Cancer Research and the chair of Breast Cancer Prevention Research at Baylor-Sammons Cancer Center and for The US Oncology Network. ‘That’s about to change very soon with the likely availability of atezolizumab [Tecentriq].’ ”
“The now-published results from the EMBRACA study confirm that talazoparib (Pfizer), a poly-adenosine diphosphate-ribose polymerase (PARP) inhibitor, prolongs progression-free survival (PFS) in patients with advanced BCRA-positive breast cancer compared with single-agent chemotherapy alone, and that it also significantly improves quality of life.
” ‘This is the largest randomized trial in BRCA mutation carriers [ever undertaken] and demonstrates PARP efficacy,’ Jennifer Litton, MD, associate professor in the Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, told Medscape Medical News in an email.”
“The use of genetic tests aimed at detecting the presence of mutations in the BRCA1 and BRCA2 genes in women with breast cancer is rapidly declining in favor of tests that can detect multiple cancer-associated mutations, according to researchers at the Stanford University School of Medicine and five other U.S. medical centers.
“Some researchers had wondered whether multigene testing, which may identify genetic mutations of uncertain clinical significance, would lead more women to consider prophylactic mastectomies — a surgery in which both breasts are removed to prevent future cancers — out of an abundance of caution. However, the current study did not show an increase in mastectomies associated with testing more genes.”
“A few months ago, olaparib (Lynparza, AstraZeneca) was the first drug approved to treat women with advanced breast cancer with germline mutations in BRCA.
“That approval was based on a significant improvement in progression-free survival (PFS) compared with standard chemotherapy shown in the OlympiAD trial. The results led to quite some excitement among breast cancer researchers, as for example in the Medscape Oncologycommentary ‘OlympiAD: Olaparib Captures Gold for BRCA-Mutated Breast Cancer Patients.’
“Now, however, a final analysis of OlympiAD results shows that overall survival (OS) did not significantly improve.”
“The FDA authorized marketing the direct-to-consumer Personal Genome Service Genetic Health Risk Report for three mutations of BRCA1 and BRCA2 most common among people of Eastern European Ashkenazi Jewish descent, according to a press release.
“The test — marketed by 23andMe — analyzes DNA using self-collected saliva samples to determine whether a woman is at increased risk for breast and ovarian cancer and whether a man is at increased risk for breast or prostate cancer.”
“The U.S. Food and Drug Administration today expanded the approved use of Lynparza (olaparib tablets) to include the treatment of patients with certain types of breast cancer that have spread (metastasized) and whose tumors have a specific inherited (germline) genetic mutation, making it the first drug in its class (PARP inhibitor) approved to treat breast cancer, and it is the first time any drug has been approved to treat certain patients with metastatic breast cancer who have a “BRCA” gene mutation. Patients are selected for treatment with Lynparza based on an FDA-approved genetic test, called the BRACAnalysis CDx.”
“Women who have BRCA mutations do just as well after treatment for breast cancer as other patients, British researchers reported Thursday.
“It’s good news for people with BRCA1 and BRCA2 mutations that raise their risk of cancer. If they get cancer and have standard treatment, they live as long as breast cancer patients without the mutation.”
“The PARP inhibitor talazoparib significantly increased progression-free survival (PFS) over physician’s choice of therapy in a randomized phase III trial of patients with advanced breast cancer and a germline BRCA mutation.
“ ‘Talazoparib is a highly potent, dual-mechanism PARP inhibitor. It prevents the repair of DNA damage, and results in cell death,’ said Jennifer K. Litton, MD, of the University of Texas MD Anderson Cancer Center in Houston. A previous phase II study showed encouraging efficacy with the agent in patients with BRCA1/2 mutations, which led to the new EMBRACA trial. Litton presented results of the trial at the 2017 San Antonio Breast Cancer Symposium (SABCS), held December 5–9.”