BRCA 1/2 Mutation Status in Breast Cancer May Not Be Predictive of Immune Response

BRCA 1/2 mutation status in patients with breast cancer may not be directly predictive of response to checkpoint inhibitor therapy, according to a new study published in Clinical Cancer Research. 
 
For the study, the researchers examined whether specific genomic markers could help guide treatment strategies in BRCA 1/2 mutation-associated breast cancers. They analyzed genomic data from the Cancer Genome Atlas and compared breast cancer with and without either germline or somatic BRCA 1/2 mutations. Using whole exome sequencing and immunohistochemistry, the researchers also studied 35 breast cancers with germline BRCA 1/2 mutations.
 
According to the press release, the study is one of the largest BRCA 1/2 breast tumor analyses to date.
 
Prior studies have hypothesized that breast cancers with somatic or germline BRCA 1/2 mutations would be more responsive to checkpoint inhibitors; however, the results of the current study showed that this may not be the case.
 
“One aspect of the study that was particularly interesting was that it builds upon our prior studies,” senior study author Katherine L. Nathanson, MD, Pearl Basser Professor for BRCA-Related Research at the Abramson Cancer Center of the University of Pennsylvania, said in the release. “Previously we found that tumors in germline BRCA 1/2 mutation carriers that did not lose the wild type allele were likely to be less sensitive to DNA damaging agents, and our new data suggests they may be more sensitive to checkpoint blockade.”
 
In this study, higher levels of genomic instability, as measured by homologous recombination deficiency (HRD), were associated with lower immunogenicity and tumor infiltration in T cells. Despite being associated with a higher mutational burden in BRCA 1/2 mutant breast cancers, HRD scores were negatively associated with expression-based immune indices.
 
“We had assumed that all BRCA 1/2 cancers with the highest HRD scores were most likely to have the strongest immune response,” study author Susan Domchek, MD, the Basser Professor in Oncology, executive director of the Basser Center for BRCA at the Abramson Cancer Center at the University of Pennsylvania, said in a press release about the findings. “But with [these] data, we now know that these assumptions were incorrect.”
 
The findings will allow researchers to move forward with examining the biological mechanisms that may inform treatment response for patients with these cancers and could further shape treatment strategies and clinical trial design for these patients, according to the study authors.
 
References
 
Kraya AA, Maxwell KN, Wubbenhorst B, et al. Genomic signatures predict the immunogenicity of BRCA-deficient breast cancer. Clinical Cancer Research. 2019. Doi: 10.1158/1078-0432.CCR-18-0468
 
Penn Research Provides Insight into Genetic Link to Potential Treatment Response Among BRCA1/2 Breast Cancer Patients [news release]. Penn Medicine. https://www.pennmedicine.org/news/news-releases/2019/may/research-provides-insight-genetic-link-to-potential-treatment-response-among-brca1-2-breast-cancer. Accessed June 4, 2019.
 
 
 



Stay up to date on the latest news in specialty pharmacy by getting Specialty Pharmacy Times in your mailbox or inbox for free!

Click here to sign up for free for the bi-monthly Specialty Pharmacy Times print journal delivered to your address.

Click here to sign up for our email newsletters delivered every Monday, Wednesday, and Friday, in addition to breaking news alerts.

Click here to follow us on Facebook. 

Click here to follow us on Twitter. 

Click here to join our LinkedIn group. 


Related Articles

The presence of human papillomavirus type 16 antibodies marked an approximately 100-fold increase in risk of throat cancer in white individuals.
Colon cancer may spread to other parts of the body before original tumors are clinically detectable.
Top news of the day from across the health care landscape.
Company Profile >
Industry Guide >
Market News >
Peer Exchange >
Conferences >
Subscribe >
Specialty Times Resources
About Us
Advertise
Careers
Contact Us
Terms & Conditions
Privacy
MJH Associates >
Pharmacy Times
OTCGuide
American Journal of Managed Care
Cure
MD Magazine
ONCLive
Targeted Oncology
Physicians' Education Resource
Pharmacy & Healthcare Communications, LLC
2 Clarke Drive
Suite 100
Cranbury, NJ 08512
P: 609-716-7777
F: 609-716-4747

Copyright Specialty Pharmacy Times 2006-2019
Pharmacy & Healthcare Communications, LLC. All Rights Reserved.
 

$vacMongoViewPlus$