CDX-011 Study Gives Triple Negative Breast Cancer Patients New Hope

“This is the most promising phase 3 trial in triple negative breast cancer in the last five years, since the phase 3 trial with the PARP inhibitor iniparib,” says Cleveland Clinic oncologist and principal investigator Alberto Montero, MD. “CDX-011 is a novel targeted drug for a disease that is defined clinically by the absence of any targets. A potent chemotherapy is delivered in a targeted fashion by being attached to an antibody that recognizes GPNMB, which is overexpressed in about 25 to 30 percent of all triple negative breast cancers.”
Click link to read full article:
http://consultqd.clevelandclinic.org/2014/11/clinical-trial-tests-targeted-breast-cancer-therapy 

All Women of Ashkenazi Descent to be Screened for the Genectic Mutations

On October 18 2014, my oncologist, Dr. Mohamed gave an excellent, very informative presentation that I attended on the risk of BRCA gene mutation of the Ashkenazi Jewish ancestry. Here listed, are some facts that I gathered from different websites that I thought was important to share with the Ashkenazi community.

Know your family history, know your risk

 

http://www.penncancer.org/basser

• Individuals of Ashkenazi Jewish ancestry (descendants from Eastern and Central Europe) have a 1 in 40 chance of carrying a BRCA gene mutation. This is at least a ten times greater probability than that of the general population.

• Women who carry mutations in BRCA1 or BRCA2 have up to an 80% risk of developing breast cancer and up to a 45% risk of developing ovarian cancer.

• The chance that breast, ovarian, or pancreatic cancers are associated with BRCA mutations is highest in families
  with Ashkenazi Jewish ancestry, multiple cases of breast cancer, women with both breast and ovarian cancer,
  breast cancer under age 50, individuals with two or more cancers, male breast cancer, pancreatic cancer or ovarian cancer at any age. 

• BRCA mutations are also associated with increased risk of fallopian tube, primary peritoneal (abdominal lining), pancreatic, melanoma, male breast and prostate cancers. 

• Men who carry BRCA mutations also have increased cancer risks.

• Men can also carry and pass these gene mutations on to their family, and also have increased cancer risk.

• If  a mother or father carries a BRCA gene mutation, there is a 50% chance of passing it on to each child. 

 

http://www.sharsheret.org

"Instead of Ashkenazi women being tested for the two defective BRCA genes only if a close blood relative contracted breast or ovarian cancer, a research team headed by Shaare Zedek Medical Center Prof. Ephrat Levy-Lahad recommends that all women of Ashkenazi origin be screened for the genetic mutations from age 30." http://www.jpost.com/Israel-News/Health/Israeli-research-team-Screen-all-Ashkenazi-Jewish-women-for-BRCA-mutations-374551 (Click link to story)

Melissa Paskvan and Dr. Mohamed

“Chemo This Morning, Garth Tonight, Enjoying The Dance."

Upfront at a Garth Brooks concert, a breast cancer survivor holds up a sign that brings Garth to a halt while singing "The Dance." Read story...
http://www.mrctv.org/blog/heartwarming-video-woman-s-sign-brings-garth-brooks-concert-halt

Congrats to the Victory Center Honored with the 2014 Debra A. Green Community Service Award...

http://thevictorycenter.org

The Victory Center's gals get-together at Toledo's Hattitude breast cancer awareness brunch hosted by Medical Mutual of Ohio on October 18th 2014. Us breast cancer survivor sisters showed our support for The Victory Center as they were recognized and honored with the Debra A. Green Community Service Award for its ongoing dedication and commitment to those touched by cancer.  This award is so very deserving to The Victory Center (TVC) as I have been a member of their breast cancer support group since 2010. I have met so many courageous survivors through TVC and the staff there, they are amazing with their compassion and commitment towards cancer patients and caregivers. Congrats to The Victory Center for this great honor! 

Melissa P., Val, Barb, Diane, Rita, Melissa J. and Jamie
4 of us are TNBC survivors!

Melissa and Dianne Cherry, Executive Director
of  The Victory Center

Dianne Cherry, Melissa, Chrys Peterson and Barb

What We Know and What We Are Learning About Triple Negative Breast Cancer 2014

Massimo Cristofanilli, M.D., F.A.C.P.

I attended an excellent TNBC presentation by Dr. Massimo Cristofanilli at the Living Beyond Breast Cancer Fall Conference on September 27, 2014, and I wanted to share with my TNBC community on "What we know and What we are learning" about Triple Negative Breast Cancer.

Triple-Negative Breast Cancer
• TNBC refers to a form of breast cancer which lacks
expression of ER, PR and HER2/neu
• It is estimated that 232,000 new cases of breast
cancer will be diagnosed in 2014
• Approximately 15-20% of breast cancers
• No targeted therapies  currently approved for TNBC
–Iniparib (not a PARP inhibitor)
–Bevacizumab (VEGF inhibitor) 

Risk factors for TNBC
• More common in young women and women of
African and Hispanic ancestry
• More common in women with a BRCA1 mutation
–75% with TNBC
• 15-20% of women with a BRCA2 mutation develop TNBC
• Patients with TNBC should consider genetic testing if
they have family history of breast/ovarian cancer or
are diagnosed at a young age 

Standard Treatments for Early-Stage TNBC
• Neoadjuvant/Adjuvant treatment
• Goal of therapy is curative
• Anthracycline and taxane-based chemotherapy
– Typically administered for 8 cycles (4 of each)
– Order doesn’t matter for adjuvant (T-(F)AC vs (F)AC-T)
– Anthracycline doesn’t matter (A vs E)
• Surgery
– Mastectomy vs Lumpectomy
• Radiation Therapy
– To breast and/or lymph nodes

Recurrence Patterns of TNBC
• Most women with metastatic TNBC are first
diagnosed with early stage breast cancer
• Recurrences are most common within 3 years of
initial diagnosis
• Metastases are more common in
–Lungs, Liver, Brain 
• Metastases are less common in
–Bone

Standard treatment for Metastatic TNBC
• Single-Agent Chemotherapy
– Taxanes
– Capecitabine   
– Eribulin      
– Liposomal doxorubicin
– Other microtubule inhibitors (ixabepilone, vinorelbine) 
• Combination Chemotherapy Regimens
– Carboplatin+Gemcitabine
– Ixabepilone+Capecitabine
• Clinical Trials
• No targeted agents are currently approved for TNBC  

What we are learning about TNBC
• Research focused on TNBC is relatively recent
• TNBC is defined by characteristics it does not have
–ER/PR negative
–HER2 negative
• TNBCs are genetically unstable
–Chromosomes are actively rearranging
–Gene alterations are ongoing
–Treatments to target this instability are being developed
• There are different types of TNBC
*** If you have a recurrence, test for subtypes to 
      determine course of treatments.

What does this mean for those with TNBC?
• Being able to subdivide triple-negative breast
cancers into subcategories will help us identify
new targets for therapy
• Clinical research is ongoing to target pathways
that are implicated in TNBC and newer trials
are being developed based on this work

Recent Clinical Trial Results
• Two randomized, phase II neoadjuvant trials presented at the
SABCS in December of 2013 demonstrated promising efficacy
for new treatments for early-stage TNBC
• Primary endpoint of study was to look at pathological
complete response rate (pCR)
• CALGB 40603
– T-AC 
– +/- bevacizumab
– +/- carboplatin
• I-SPY2
– T-AC
– +/- carboplatin plus veliparib (ABT-888)

Summary of Results
• CALGB 40603
–Addition of bevacizumab lead to increased in breast pCR rates
but not in breast+axilla
–Addition of bev lead to an increase in serious toxicities
–Addition of carbo lead to significant increases in pCR rates in
breast and axilla, with increased but manageable toxicities
• I-SPY2
–TAC +/- (veliparib+carboplatin)
–Estimated pCR rate for veliparib+carbo predict a high likelihood
of success over control arm
–Veliparib/carbo arm associated with higher rates of hematologic toxicity

Role of Carboplatin and Veliparib in TNBC
• Both CALBG 40603 and I-SPY2 suggest a role for carbo in the
management of a subset of TNBCs
• While carbo did increase risk of hematologic toxicities, these
toxicities were manageable (delays, dose mods)
• Addition of bev only seemed to increase in breast pCR rates,
but at the risk of life-threatening toxicities
• Contribution of veliparib is unclear
• A phase III study investigating the contribution of carbo and
carbo/veliparib for women with early stage breast cancer will
be opening soon
• A phase II neoadjuvant study is currently ongoing at TJU

Targeted Therapies Currently Under Investigation for Advanced TNBC
• Immune therapy (PD-1/PD-L1 inhibitors) +/- chemotherapy
• Androgen receptor
• PARP inhibitors
– Mutation carriers (monotherapy)
– TNBC (in combination with chemo)
• GPNMB
• Glucocorticoid receptor
• AKT/PI3K/mTOR inhibitors
• Jak2 inhibitors
• Macrophages (the tumor microenvironment) 

Why has it been so hard to find a treatment?
• TNBC is not one disease 
–It is important to understand which type of TNBC will
respond to which type of therapy
• Tumors are genetically unstable and are constantly
undergoing changes
• Newer technologies and clinical trials hold great
promise for the future

Future Promise
• Much research is ongoing in the field of breast cancer
–Understand mechanisms of resistance
–Develop more personalized therapy
• New therapies are being developed and tested in
clinical trials specifically for TNBC
• Hope for the future
–More effective therapies
–Fewer side effects 

Dr. Cristofanilli taking questions from the audience of
mostly TNBC Survivors. Seated on the left is Arlene Brothers of
the Triple Negative Breast Cancer Foundation