New Posts New Posts RSS Feed - New Genes Implicated in TNBC
  FAQ FAQ  Forum Search   Events   Register Register  Login Login

New Genes Implicated in TNBC

 Post Reply Post Reply
Author
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 13143
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Topic: New Genes Implicated in TNBC
    Posted: Aug 19 2019 at 11:20pm

Dr. Fergus Couch on New Genes Implicated in Triple-Negative Breast Cancer Risk



The link is to a video of Dr. Couch talking about the research findings and implications in the African American population.  More TNBC shows up in this population and there's a strong association.  More precision risk assessment is needed in the African American population, whereas before they were just borrowing the risk assessment from the Caucasian population and they have found out there isn't a direct correlation.

Understanding Breast Cancer Risk Genes

team of researchers in Rochester, Minnesota recently discovered mutations in 5 genes that seem to increase the risk for TNBC. These genes are known by several names: breast-cancer-risk genes, cancer-predisposition genes, and cancer-susceptibility genes. The research team was led by Fergus J. Couch, PhD, the Zbigniew and Anna M. Scheller Professor of Medical Research and Chair of the Division of Experimental Pathology and Laboratory Medicine at the Mayo Clinic. 

About the Study

About 10 to 15% of triple-negative breast cancers in Caucasians test positive for mutations in the BRCA1 gene. In the African American population, about 35% test positive.

Until recently, BRCA1 was the only gene linked to TNBC. In the past, researchers weren’t able to find other breast cancer risk genes, because the technology was too complicated to check the genes in large numbers of people, Couch says.

“We used to check one gene at a time, which was very time consuming. But about 4 or 5 years ago, sequencing technology changed dramatically, so now we’re able to do these gene panels and check many genes at a time.”

Couch and his research team used a technology called multigene panel testing on blood samples taken from people with triple-negative breast cancer. The technology looks at multiple genes at once, looking for mutations that could be linked to breast cancer.

The team studied how often mutations occurred in people with TNBC compared with a control group of people who didn’t have cancer. This was the first study to find mutated genes that are linked to an increased risk for TNBC. They are: BARD1, BRCA1, BRCA2, PALB2, and RAD51D.

Women who carried any of these gene mutations had a more than 20% lifetime risk for any type of breast cancer. By comparison, women in the general population have about a 12% —or 1 in 8—lifetime risk of getting breast cancer.

“That means,” Couch says, “doctors should consider that women who have any of these mutations will have an increased risk for triple negative breast cancer. Also if a woman with breast cancer has one of these mutations, her doctor may need to consider using specific treatments.

The team was not able to learn why African American women have an increased risk for TNBC, and they suggest that larger studies with African American patients be done.

The team also found strong support that 3 other mutated genes (BRIP1, RAD51C, and RAD51D) moderately increase the risk for TNBC, when they were previously thought to only be associated with ovarian cancer.

Why It's Called Triple Negative

Breast cancers are mainly classified by 3 proteins that can affect the cancer’s growth:

  1. The estrogen receptor
  2. The progesterone receptor
  3. The human epidermal growth factor receptor 2 (HER2)

Estrogen and progesterone hormones attach to their specific receptors on the cancer and help breast cancer grow (hormone-positive). One-third of breast cancers make too much of the HER2 receptor which causes them to grow very quickly (HER2-positive).  

However, if the cancer doesn’t have the estrogen and progesterone receptor (hormone-negative) and doesn't make too much of the HER2 receptor (HER2-negative), it is called triple negative breast cancer.

Triple-negative breast cancers grow and spread more quickly than most other types of breast cancer. Since the cancer cells don't have hormone receptors, hormone therapy won't work for these cancers. And because they don't have much HER2, drugs that target HER2 aren't helpful, either. Chemotherapy is usually the standard treatment. 

What the Results Could Mean

With the identification of these TNBC genes, doctors can use genetic tests that include this set of genes to find patients with an increased risk for TNBC. Finding these TNBC genes also allows researchers to focus on developing drugs that could target specific mutations in tumors.

New guidelines for gene testing for those at risk for triple-negative breast cancer. Current guidelines from the National Comprehensive Cancer Network (NCCN) recommend that people be tested for BRCA1 and BRCA2, if they have an increased risk for breast cancer due to multiple reasons including a personal or family history of cancer such as:

  • A family history of breast or ovarian cancer
  • A diagnosis of TNBC at age 60 or younger
  • A diagnosis of breast cancer at age 50 or younger

Additional guidelines to test patients for genes other than BRCA1 or BRCA2 may become available as more breast cancer risk genes are found.  

Plus, only mutations in certain genes qualify women for breast MRI in addition to mammograms for screening and early cancer detection. Some of the genes found by Couch are not currently on that list. “The hope is that breast cancer screening guidelines might change based on our findings,” Couch says. “Those at high risk could then get additional screening with a breast MRI, which studies show can improve survival,” he says.

Drugs for treatment of people who have gene mutations (called mutation carriers) and for those who have been diagnosed with triple-negative breast cancer. Couch explains that now that we better understand the genes associated with a risk for TNBC, we can start testing current targeted therapy drugs. For instance, there’s some evidence that BRCA1 and BRCA2 carriers with TNBC might respond well to platinum drugs, such as cisplatin or carboplatin.

People with certain gene mutations may also be helped by a type of drug called PARP inhibitors. PARP is a protein that helps both healthy and cancer cells repair DNA damage so they can live. PARP inhibitors work by blocking PARP proteins in cancer cells. That prevents them from repairing DNA damage, and often leads to their death.

Some of the new TNBC genes work the same way as BRCA1 and BRCA2, so studies are underway to learn if tumors with these gene mutations might also benefit from platinum drugs or PARP inhibitors.

https://www.cancer.org/latest-news/study-newly-identified-genes-risk-triple-negative-breast-cancer.html




Edited by 123Donna - Aug 22 2019 at 11:49am
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

Back to Top
Kellyless View Drop Down
Senior Member
Senior Member


Joined: Jun 18 2009
Location: Dallas, Texas
Status: Offline
Points: 1077
Post Options Post Options   Thanks (0) Thanks(0)   Quote Kellyless Quote  Post ReplyReply Direct Link To This Post Posted: Aug 20 2019 at 4:35pm
What's "new"? I was tested for these 3, three years ago. I had done BRCA1 & 2 ten years ago. My friend was diagnosed with BARD 2 1/2 years ago, she opted for mastectomy and hysterectomy because of it. I guess my point is, if you were genetically tested because of TNBC in the last 3 years you were probably tested for these 5 mutations. 

Edited by Kellyless - Aug 20 2019 at 4:35pm
IDC, 2.2 cm, Stage IIb,lumpectomy 1/30/09 ACx4,Tx4 36 rads
6/1/16 Local recurrence same breast, same spot 1.8cm Carb.4x every 3 wks, Taxol 12x once wk. Dbl Mast. PCR!! Reconstruction fail, NED!
Back to Top
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 13143
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Aug 20 2019 at 8:31pm
Kelly,

The first link is to a video of Dr. Couch talking about the implications in the African American population and more TNBC that shows up with this population and it's strong association.  More precision of risk assessment in the African American population whereas before they were just borrowing the risk assessment from the Caucasian population and there isn't a direct correlation.
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

Back to Top
 Post Reply Post Reply
  Share Topic   

Forum Jump Forum Permissions View Drop Down

Forum Software by Web Wiz Forums® version 12.01
Copyright ©2001-2018 Web Wiz Ltd.