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CATEGORIES [ SABCS2012, BREAST CANCER ]

A recap of triple-negative breast cancer research from San Antonio

BY GUEST BLOGGER | DECEMBER 9, 2012

The best news from the 2012 San Antonio Breast Cancer Symposium is its emphasis on triple-negative breast cancer. There are so many papers presented on the subject that I can't keep up. Those of us who have been hanging around this dance for a long time--I was diagnosed in 2006--remember the frustration of seeing and hearing little about this disease from researchers and nothing from the media, who simply didn't appear to comprehend the complexity of breast cancer as a whole and were unaware that there was a type not fueled by estrogen or progesterone. And HER2? What's that?

That is changing. More than 82 clinical trials are now looking for targeted treatments for TNBC. Because TNBC is defined by what it lacks--receptors for estrogen, progesterone and HER2/neu--it also lacks a targeted therapy. Researchers are busy finding a genetic signature of subsets of TNBC that will lead to those therapies.

The San Antonio symposium this year had at least 20 papers looking at the genetics of TNBC, its response to chemo, and the potential for those targeted drugs, which no longer look as elusive as they had once been.

The highlights of research presented on TNBC this year:

Androgens
Some 75 percent of all breast cancers and 10 to 20 percent of triple negative cancers are positive for the androgen receptor. Several research studies have looked at the influence of androgen receptors on TNBC, which means new treatments plus a broader and deeper understanding of the disease. TNBC cancers that are also positive for androgen receptors are molecularly similar to prostate cancer and could potentially be treated similarly.

AR-positive tumors responded well to bicalutamine and to 17-DMAG, a drug that has been recently in clinical trials, according to research presented by Jennifer Pietenpol, PhD, director of the Vanderbilt-Ingram Cancer Center.

A phase 1 clinical trial at the University of Colorado has been studying the effectiveness of enzalutamide, a drug used to treat prostate cancer, on triple-negative. A phase 2 trial is planned at Colorado, Memorial Sloan-Kettering Cancer Center and the Karmanos Cancer Institute.

A Heterogeneous Disease
It is increasingly clear that TNBC is not one disease, but a family of diseases, some of which are highly aggressive, and some that are not aggressive at all. We're getting increasingly closer to knowing which ones are which.

"This heterogeniety highlights the need for personal medicine," said Justin M. Balko, PharmD, PhD, research faculty in the laboratory of Carlos Arteaga, MD, at the Vanderbilt-Ingram Cancer Center in Nashville, Tenn. Balko's research looked at how TNBC tumors changed genetically after neoadjuvant chemotherapy, and highlighted frequent mutations and amplifications, including the novel JAK2 genetic mutation, that can lead future research and the development of TNBC-specific drugs.

The JAK2 gene has not been observed in previous research, Balko said. The patients in the study who had the JAK2 amplification tended to have a poor prognosis, which means that JAK2 may be a key to which cases of TNBC are aggressive and which aren't. Those with JAK2 expression may respond to inhibitors currently in clinical trials for inflammatory diseases, Balko said, which could be a game changer.

In both Pietenpol and Balko's presentations, each TNBC tumor was unique, with different mixtures of similar mutations and amplifications. While TNBC tumors might share a tendency toward specific genetic mutations, the way those mutations play out differs from tumor to tumor, and may even change during treatment. Both studies showed a frequent mutation of the TP53 tumor suppressor in TNBC tumors.

Response to Chemotherapy
Breast cancer might be biologically different in very young women versus older women, according to Sibylle Loibl, MD, PhD, associate professor at the University of Frankfurt in Germany. This may explain why younger women tend to respond better to neoadjuvant chemotherapy than older women, achieving a complete pathological response more often that older women. A pathological complete response is associated with a much better prognosis.

And in a phase 3 multicenter study, women with metastatic TNBC had a more significant response to treatment with eribulin versus capecitabine, with a median overall survival of 14.4 months with eribulin compared with 9.4 months with capecitabine. The survival line for metastatic TNBC extended beyond six years.

Most Women Survive
The great majority of women with local and regional recurrences survive after five years with proper treatment. Women with estrogen-negative breast cancer benefited the most if that treatment included chemotherapy after surgery, according to the Chemotherapy as Adjuvant for Locally Recurrent Breast Cancer (CALOR) trial. Researchers reported a 67 percent disease-free survival rate after five years for those who received chemotherapy versus 35 percent for those who did not, and a 79 percent overall survival rate after five years for those who received chemotherapy and 69 percent for those who did not. A big takeaway here is that local and regional recurrences--near the site of the original primary tumor and in the lymph nodes--are highly treatable.

In the BEATRICE phase 3 trial, some 87 percent of TNBC patients with stages 1, 2 and 3 TNBC treated with current chemotherapy survived disease-free.

Such positive results are becoming common for TNBC, said Kent Osborne, MD, director of the Dan L. Duncan Cancer and the Lester and Sue Smith Breast Center at Baylor College of Medicine in Houston, Texas. "We're seeing this across the board."

Patricia Prijatel is the author of Surviving Triple-Negative Breast Cancer and The Magazine from Cover to Cover, both published by Oxford University Press, and the founder and editor of the Positives About Negative blog. She is the E.T. Meredith Distinguished Professor Emerita, the former director of the School of Journalism and Mass Communications, and founder of the E.T. Meredith Center for Magazine Studies at Drake University.

Patricia Prijatel

RELATED POSTS

COMMENTS

THIS GAVE ME SUCH HOPE THANK YOU FOR POSTING THIS NOW I CAN ENJOY XMAS SOMETIMES WE JUST NEED A LITTLE HOPE,
- Posted by becky keech 12/11/12 7:47 AM

Such a great article and vextremely exciting to see SOoo much emphasis on TNBC! I will be watching for additional recaps from you!!!!
- Posted by Georgia 12/11/12 4:49 PM

This article is soooooo inspiring!! Tnbc is now being recognized as a treatable disease....and praying curable someday!! Such hope exists for so many!! :)
- Posted by michelle 12/12/12 7:18 AM

this aeticle is wonderful! always hope. l loved your book
- Posted by denise 12/13/12 9:08 AM

Hi I am concerned about this article as I feel it gives false hope. The statistics look wrong. Please check. 87% of TNBC patients do not live 5 years. It is a great deal lower than that.
- Posted by Alison 12/14/12 3:16 AM

I've just had a recurrence of tnbc, so I'm hopefull that there will be a cure in our lifetime!
- Posted by Donna Goulet 12/14/12 1:33 PM

Nice to hear more hopeful news right before the holidays. Thank you.
QR5EJ2N
- Posted by Cindy 12/15/12 6:11 AM

I had TNBC in early 2007 - stage 1B. I agonized over whether to take chemo but since it was 9 out of 9 aggressive decided to do it.
As of now, 5 1/2 yrs later, I am cancer free and so happy to read that there is more attention to this type of Breast Cancer. Thanks for your advocacy -By the way - I am a Drake graduate also!!
- Posted by Dalya 12/15/12 6:59 AM

My beloved wife was diagnised TNBC T1N0M0 on 21/07/2011. After receiving chemo-radio treatment is thank god still cancer free, having a very happy life after reaccessing her values of life. Not only her but at least 3 more women who we met during therapy are still cancer free. I personaly believe that positive thinking is as important as many of the therapies
- Posted by Angelo Polychronis 3/5/13 3:36 AM

I was diagnosed with TNBC stage III July 2011. I had wide local excission, follwed by 6 rounds of FEC chemo and 30 rounds of radio. That took me to May 2012. I found a new lump christmas and 2 weeks ago was told that the cancer has returned.facing a double mastectomy and more chemo......however Just wanted to say having read this It has given me renewed hope.
Have bone scan and CT later this week, hoping for the best, however as the tumour has never showed on any Imaging ie mamo, ultrasound, mri etc...Iv no confidence In It showing up anywhere else If It has spread only seems to show Iself wnen biopsy Is done......anyway the battle begins again.
- Posted by nicola 3/18/13 10:53 AM

In October 2001 at age 51 I was diagnosed with Stage 3C TNBC. I underwent a radical mastectomy. I was put into a Clinical Trial involving 8 chemo and 34 radation treatments finally completing all in August of 2002. At that time no one had any real information to share. It so encouraging to see that there is finally extensive research being done into TNBC and they are finally getting a clearer picture of what it is. I thank God everyday for the care that I received and the fact that I have remained cancer free.
- Posted by Gerri 5/16/13 7:37 AM

Late Nov 2011, my wife (age 50) was diagnosed with TNBC.

Dec 2011: Sentinal lymph node involved; removed 11 other nodes, all negative.

Jan 2012: Began 6 months (every 3 wks) of adjudant chemo treatment. Mid-way, the lump was growing, so she had double radial mastectomy, then finished up chemo. Pathology showed the overall mass had grown, but the tumor had been shrinking. The doctors decided it would not be necessary to do radiation after chemo. Last round of chemo was the end of July 2012.

Nov 2012: attempted reconstructive surgery, but got severely infected and had to reverse the procedure in mid-December 2012.

April 2013: my wife noticed a lump growing, but doctors all said it was just fluid build-up from the reconstruction reversal surgery. Full-body PET scan showed nothing, MRI showed nothing, blood counts all normal, needle biopsy showed nothing. She remained concerned about the lump (good thing). For her peace of mind, the dr. ordered a mamogram and sonogram.

May 2013: a mamogram showed a problem needing immediate follow-up; an ultrasound the same day showed the lump had a blood supply and confirmed solid mass - NOT liquid build-up! Two days later, she had a lumpectomy. Pathology confirmed it was repeat TNBC (5.1 cm). She will start chemo again as soon as she has healed from the surgery, followed by 7 weeks of radiation.

Praying for the best, preparing for the worst. However, we are convinced that God is GOOD...ALWAYS. We praise His Name, knowing He has a plan and purpose.
- Posted by Eric 6/3/13 12:08 PM

I was just googling my moms name and found her comment, her name is Becky keech. She did get to enjoy her Christmas last year, unfortunately her TNBC returned and spread 7 months later and she passed on sept. 2nd. I am thankful your article helped her get through last Christmas. I miss her soooo much it hurts.
- Posted by karrie lohr 10/4/13 10:51 PM

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