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"I promise, Suzy... Even if it takes the rest of my life." - Nancy G. Brinker, founder of Susan G. Komen for the Cure

What is Triple Negative Breast Cancer?


Just in recent years, Triple Negative Breast Cancer has sparked interest in the news where instead of calling the tumor as ER-negative, PR-negative, and HER2-negative; researchers began using the shorthand term, "Triple Negative," dubbed the "new type" type of cancer. Being Triple Negative, you don't have a targeted therapy and that your only treatment option is chemotherapy.

Triple Negative is seen in about 15% of all breast cancers. Triple Negative is a very aggressive cancer that tends to strike younger women, pre-menopause, especially among African-American women and women who have BRCA1 mutations. The tumor tends to be fast growing and is less likely to show up on an annual mammogram. TN is more likely to metastasis early on; has a high rate of recurrence in the first 2-3 years from diagnosis and has a poorer prognosis than other types of breast cancer due to lack of specific, targeted treatment for TNBC.

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Tuesday, November 4, 2014

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

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)
• 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


  1. Thank you for sharing this information. I am also a TNCB patient and just finished my treatments. Thank you for this blog! I appreciate your effort in keeping readers like me informed.

    1. KaYee, Congrats on finishing your treatments.... You're on your way to a healthy life again :) Stay positive and live life today.


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