Beyond BRCA: Links between breast, second primary cancer and inherited mutations

May 31, 2018, Perelman School of Medicine at the University of Pennsylvania

Rates of inherited mutations in genes other than BRCA1/2 are twice as high in breast cancer patients who have had a second primary cancer—including, in some cases, different types of breast cancer—compared to patients who have only had a single breast cancer. But the rates of these mutations were still found to be low overall, meaning it's difficult to assess whether and how these individual mutations may drive the development of cancer. The study from the Basser Center for BRCA in the Abramson Cancer Center of the University of Pennsylvania also investigated the use of polygenic risk scores—which have recently been added to some commercial clinical multiplex genetic testing panels. Kara N. Maxwell, MD, Ph.D., an instructor of Hematology-Oncology and the study's lead author, will present the findings at the 2018 American Society of Clinical Oncology Annual Meeting in Chicago (Abstract #1503).

Genetic testing can help identify have a genetic predisposition that puts them at risk for developing . Recently, new therapies called PARP inhibitors have been FDA approved to specifically target cancers caused by certain —such as BRCA1/2, which carry a lifetime cancer risk of as much as 85 percent and 50 percent for ovarian cancer, as well as higher risks of pancreatic, prostate and other cancers.

"We need to gain a better understanding of why patients who have multiple cancers may be susceptible to them, and that work needs to go beyond the common genes we're already been looking at," Maxwell said.

The team—led by Susan M. Domchek, MD, executive director of the Basser Center for BRCA, and Katherine L. Nathanson, MD, deputy director of the Abramson Cancer Center, specifically looked at patients who did not have a BRCA1/2 mutation and tested them for a panel of 15 different genetic mutations. They evaluated 891 patients who had a second primary cancer—breast or otherwise—after initial breast cancer and compared them to 1,928 who only had a single breast cancer. About eight percent of patients who had second primary cancers had mutations, compared to just four percent of patients from the single cancer cohort. The current threshold for whether or not genetic testing is recommended is five percent.

"Our data show that patients who have had multiple primary cancers should undergo genetic testing, and likely this holds true for a number of other types of second cancer," Maxwell said. "However, the overall numbers are still low, which shows the level of uncertainty that still exists and highlights the need for further research."

The research also evaluated polygenic risk scores, a somewhat controversial metric recently added to some commercial clinical multiplex panels. Polygenic risk scores are determined by how many single nucleotide polymorphisms (SNPs) a person has. SNPs are common variants with smaller effect sizes, and if a patient has multiple of certain SNPs, they may be at a similar increased for cancer a as patients with a single rare mutation.

"Our study does not provide strong evidence of higher polygenic risk scores in patients with more than one ," but many more patients will need to be studied to confirm this," Maxwell said.

Explore further: Risk of a second breast cancer can be better quantified in women carrying a BRCA mutation

More information: Maxwell will present the findings as an oral abstract in the Cancer Prevention, Hereditary Genetics, and Epidemiology session on Sunday, June 3rd, at McCormick Place in Room S404 at 9:00 AM Central.

Related Stories

Risk of a second breast cancer can be better quantified in women carrying a BRCA mutation

March 21, 2018
The risk of a second breast cancer in patients with high-risk BRCA gene mutations can be more precisely predicted by testing for several other genetic variants, each of which are known to have a small impact on breast cancer ...

Breast cancer genes a real risk for men, too

April 26, 2018
(HealthDay)—Few American men are screened for gene mutations that can greatly increase their risk of breast and other types of cancers, a new study reveals.

Busting myths surrounding cancer and genetic testing

April 13, 2018
(HealthDay)—While only 5 percent to 10 percent of cancers are caused by an inherited gene mutation, genetic testing may benefit people with a strong history of family cancer, an expert in genetics suggests.

Genetic predisposition to breast cancer due to non-brca mutations in ashkenazi Jewish women

July 20, 2017
Genetic mutations in BRCA1 and BRCA2 increase the risk of breast and ovarian cancer in Ashkenazi Jewish women. A new article published by JAMA Oncology examines the likelihood of carrying another cancer-predisposing mutation ...

Males with BRCA mutations have increased risk of certain cancers

April 17, 2018
(HealthDay)—Males with BRCA mutations have increased incidence of malignant disease, specifically prostate, melanoma, pancreas, and breast cancers, according to a research letter published online April 12 in JAMA Oncology.

Ovarian cancer drug shows promise in pancreatic cancer patients with BRCA mutation

May 17, 2018
A targeted therapy that has shown its power in fighting ovarian cancer in women including those with BRCA1 and BRCA2 mutations may also help patients with aggressive pancreatic cancer who harbor these mutations and have few ...

Recommended for you

Targeting the engine room of the cancer cell

June 18, 2018
Researchers at Columbia University Irving Medical Center (CUIMC) have developed a highly innovative computational framework that can support personalized cancer treatment by matching individual tumors with the drugs or drug ...

Researchers create novel combination as potential therapy for high-risk neuroblastoma

June 18, 2018
Researchers at VCU Massey Cancer Center in Richmond, Virginia, have identified a promising target to reverse the development of high-risk neuroblastoma and potentially inform the creation of novel combination therapies for ...

Study suggests well-known growth suppressor actually fuels lethal brain cancers

June 18, 2018
Scientists report finding a potentially promising treatment target for aggressive and deadly high-grade brain cancers like glioblastoma. But they also say the current lack of a drug that hits the molecular target keeps it ...

Standard myelofibrosis drug can awaken 'dormant' lymphoma

June 18, 2018
Most patients with myelofibrosis, a rare chronic disorder of the haematopoietic cells of the bone marrow, benefit from drugs from the JAK2 inhibitor class: symptoms are relieved, survival extended and general quality-of-life ...

Genomics offers new treatment options for infants with range of soft tissue tumors

June 18, 2018
The genetic causes of a group of related infant cancers have been discovered by scientists at the Wellcome Sanger Institute, the University of Wuerzburg and their collaborators. Whole genome sequencing of tumours revealed ...

Breast cancer researcher warns against online genetic tests

June 18, 2018
We have never been so fascinated by the secrets inside our cells.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.