A New Era Of Hope For Patients With Triple
Triple-negative breast cancer is a particularly devastating subtype of breast cancer, as it is often diagnosed in young women and is associated with an exceptionally poor prognosis. The triple-negative designation indicates that the three key features driving most breast cancers are lacking, but it provides no clues as to potential biologic drivers. In the absence of any biologic insights, tailored, targeted treatment decisions have historically not been possible.
Consequently, until as recently as 2018, we have relied exclusively on nonselective cytotoxic agents, with modest success. For example, conventional neoadjuvant chemotherapy confers a pathologic complete response in just 50% to 55% of patients with early-stage triple-negative breast cancer,1-4 and among those who do not achieve a pathologic complete response, approximately one-third will die within 3 years.5 Moreover, patients with metastatic triple-negative breast cancer treated with conventional chemotherapeutics have a median survival of 12 to 18 months and an estimated 5-year overall survival of 11%.6 Thus, therapeutic innovation for early and late triple-negative breast cancer has been desperately needed.
Biologic Insight Leads to Therapies
From biologic insight springs hope for therapeutic innovation. Heather L. McArthur, MD, MPHTweet this quote
Immune Modulation Via Checkpoint Blockade
Antibody-Drug Conjugates
Forecast Finally Changing in Triple-Negative Disease
REFERENCES
New Treatment Approach For Rare Type Of Triple Negative Breast Cancer Identified
In a new study, published in journal Clinical Cancer Research, researchers at the charitys centre at The Institute of Cancer Research, London, demonstrated in cell-lines and in mice that palbociclib could be used effectively to treat certain triple negative breast cancers opening the door to an exciting new use for this first-in-class drug, which now needs to be trialled in patients.
Triple negative actually represents a diverse group of subtypes of the disease that lack the three molecules typically used to classify breast cancers: the oestrogen receptor , progesterone receptor , and human epidermal growth factor receptor 2 . TNBCs tend to exhibit aggressive behaviour and are more likely to spread to another part of the body, becoming incurable and they are more likely to be diagnosed in black women than Caucasian women.
A subset of these TNBCs are known to have cells which produce androgen receptors and are therefore known as Luminal Androgen Receptor breast cancers.
It is estimated that around 1,000 women each year in the UK are diagnosed with LAR triple negative breast cancer which accounts for around 2% of all breast cancers. This form of breast cancer cannot be treated with targeted drugs commonly used to treat other types, such as tamoxifen and aromatase inhibitors or Herceptin .
Baroness Delyth Morgan, Chief Executive at Breast Cancer Now, which funded the study, said:
Tnbc Chemotherapy Drugs And Efficacy Evaluation
Compared to other types of breast cancer, TNBC has limited treatment options, is prone to recurrence and metastasis, and has a poor prognosis. The main reason is that the expression of ER, PR, and HER2 are all negative, making specific endocrine therapies and targeted therapies ineffective. Therefore, chemotherapy has become the main approach for the treatment of TNBC. In recent years, a large body of literature has shown that the use of neoadjuvant chemotherapy regimens in the treatment of TNBC has a significantly higher pathological remission rate than for hormone receptor-positive breast cancer and can significantly improve the prognosis of TNBC patients. The national comprehensive cancer network guidelines recommend using combination regimens based on taxane, anthracycline, cyclophosphamide, cisplatin, and fluorouracil. At present, taxel/docetaxel + adriamycin + cyclophosphamide , docetaxel + cyclophosphamide , adriamycin + cyclophosphamide , cyclophosphamide + methotrexate + fluorouracil , cyclophosphamide + adriamycin + fluorouracil , and cyclophosphamide + epirubicin + fluorouracil + paclitaxel/docetaxel are the preferred adjuvant regimens for TNBC. Therefore, the selection of appropriate chemotherapy drugs and the optimization of chemotherapy regimens are important for ensuring good treatment outcome and prognosis of TNBC patients.
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Is Triple Negative Breast Cancer The Worst
Triple negative breast cancer is considered an aggressive cancer because it grows quickly, is more likely to have spread at the time its found and is more likely to come back after treatment than other types of breast cancer. The outlook is generally not as good as it is for other types of breast cancer.
Triple Negative Breast Cancer Clinical Trial
Ongoing clinical trial tried to investigate effectiveness and safety of different possible treatment for future use and also has several clinical trials in the pipeline. The patient can also enroll their name in these trials to get novel therapies and also assist in research by providing the data to the research team. The different research aim is different, some are investigating new therapies to treat the patient, whereas some drugs may use in preventive therapy. Name registration for a clinical trial is the first step to enrolling name to the research3,4.
References
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How Common Is Triple Negative Breast Cancer
15% of all breast cancers over 8,000 cases a year in the UK are triple negative.
Triple negative breast cancer is more common in:
- women who have inherited an altered BRCA gene
- black women
- women who have not yet reached the menopause
- women under 40
Some types of breast cancer are more likely to be triple negative than others. These include medullary and metaplastic breast cancer. However, most people with triple negative breast cancer have invasive ductal breast cancer as this is the most common type of breast cancer in general.
Relieving Symptoms Of Advanced Breast Cancer
Treatment to relieve symptoms depends on where the cancer has spread. For example, pain from bone metastases may be treated with radiation therapy, drugs called bisphosphonates such as pamidronate or zoledronic acid , or the drug denosumab . For more, see our information about the treatment of bone metastases.
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Brca1 Inherited Gene Mutations And Tnbc
Most breast cancers related to a BRCA1 inherited gene mutation are both triple negative and basal-like .
TNBC may also be related to a BRCA2 inherited gene mutation .
The National Comprehensive Cancer Network recommends people diagnosed with TNBC at age 60 or younger get genetic testing .
Learn more about genetic testing.
Progression While Being Treated With Hormone Therapy
For hormone receptor-positive cancers that were being treated with hormone therapy, switching to another type of hormone therapy sometimes helps. For example, if either letrozole or anastrozole were given, using exemestane, possibly with everolimus , may be an option. Another option might be using fulvestrant ;or an aromatase inhibitor , along with a CDK inhibitor. If the cancer has a PIK3CA mutation;and has grown while on an aromatase inhibitor, fulvestrant with alpelisib might be considered. If the cancer is no longer responding to any hormone drugs, chemotherapy is usually the next step.
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Tnbc Subtyping And Treatment Regimens
In 2011, Lehmann et al. performed gene expression profiling of tumor samples from 587 TNBC patients and divided TNBC into six subtypes: basal-like 1 , basal-like 2 , mesenchymal , mesenchymal stem-like , immunomodulatory , and luminal androgen receptor . They also performed gene profiling and compared existing TNBC breast cancer cell lines, classifying them into six different subtypes, thus providing an accurate cell model for clinical treatment of TNBC .
Table 1 Genomic TNBC subtypes and assignment of TNBC cell lines to subtypes
Determining Risk Of Recurrence In Triple
A personalized prognosis for patients diagnosed with triple-negative breast cancer was the goal of a new study by Katherine Varley, PhD, researcher at Huntsman Cancer Institute and assistant professor of oncological sciences at the University of Utah.;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;
Twenty percent of women diagnosed with breast cancer in the United States will learn they have triple-negative breast cancer. That diagnosis means the three most common proteins known to fuel breast cancer growthestrogen receptor, progesterone receptor, and HER2are not present in the tumor. Those patients will not respond to any of the targeted therapies developed to treat breast cancer with those characteristics. After surgery, their only treatment option is chemotherapy. Targeted therapy allows healthy cells to survive, but chemotherapy can kill normal cells when eliminating the cancer cells.
Varley worked closely on the study with Rachel Stewart, DO, PhD, assistant professor of pathology and laboratory medicine at the University of Kentucky. They used specimens from patients treated at HCI. The tumor samples were taken more than five years ago, so the researchers could determine how each patient fared in the long term. The next step was developing a way to test for biomarkers of the immune response. The biomarker test was developed using formalin-fixed, paraffin-embedded tissues. This is important because it means this test can be run on tumor biopsy specimens that are routinely collected for breast cancer diagnosis. ;
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A Note About Statistics
Survival rates are statistics, and as such tend to tell us how the “average” person will do with an “average” triple-negative breast cancer; but people and tumors aren’t statistics. Some people will do better and some people will do worse.
Very importantly, statistics are usually several years old. In order to calculate five-year survival rates, a person would have to have been diagnosed at least five years prior. And still there is lag time. The treatment of triple-negative breast cancer is changing, and new drugs have been approved.
Mercks Keytruda Plus Chemotherapy Reduced Risk Of Death By 27% Versus Chemotherapy As First
First Anti-PD-1 Therapy in Combination With Chemotherapy to Demonstrate Statistically Significant Overall Survival for These Patients
Data From Phase 3 KEYNOTE-355 Trial Presented at ESMO Congress 2021
KENILWORTH, N.J.—-Merck , known as MSD outside the United States and Canada, today announced the final overall survival results from the pivotal Phase 3 KEYNOTE-355 trial investigating KEYTRUDA, Mercks anti-PD-1 therapy, in combination with chemotherapy for the first-line treatment of patients with metastatic triple-negative breast cancer . KEYTRUDA is the first anti-PD-1 therapy in combination with chemotherapy to demonstrate a statistically significant and clinically meaningful improvement in OS for these patients.
In this study, KEYTRUDA plus chemotherapy reduced the risk of death by 27% in patients with mTNBC whose tumors expressed PD-L1 , as compared to chemotherapy alone. There was an increase of 6.9 months in median OS with KEYTRUDA plus chemotherapy compared to chemotherapy alone . Although the trial was not powered to compare efficacy between treatment groups by different chemotherapy regimens, the increase in OS was observed for KEYTRUDA plus chemotherapy across the three chemotherapy choices. These data were presented today in an oral presentation at the European Society for Medical Oncology Congress 2021 .
About KEYNOTE-355
About Triple-Negative Breast Cancer
About KEYTRUDA® Injection, 100 mg
Selected KEYTRUDA® Indications in the U.S.
Melanoma
Gastric Cancer
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Advanced Cancer That Progresses During Treatment
Treatment for advanced breast cancer can often shrink the cancer or slow its growth , but after a time, it tends to stop working. Further treatment options at this point depend on several factors, including previous treatments, where the cancer is located, and a woman’s age, general health, and desire to continue getting treatment.
Early Detection May Save Your Life
Frequency as it relates to your age and medical history should be discussed with your physician.
The symptoms of breast cancer do not present themselves outwardly on any relevant timescale.
Unfortunately, when the media focuses greatly on a new infectious condition, breast cancer screenings tend to drop and may drop quite a bit meaning, theres a lot of cancer in a lot of boobs thats festering and growing secretly.
Though the death rate has been dropping slightly, by about 1.3% per year, the number of diagnosed cases is actually going up!
So while deaths attributed to breast cancer are declining, cases of breast cancer are not.
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Do I Need Genetic Counseling And Testing
Your doctor may recommend that you see a genetic counselor. Thats someone who talks to you about any history of cancer in your family to find out if you have a higher risk for getting breast cancer. For example, people of Ashkenazi Jewish heritage have a higher risk of inherited genetic changes that may cause breast cancers, including triple-negative breast cancer. The counselor may recommend that you get a genetic test.
If you have a higher risk of getting breast cancer, your doctor may talk about ways to manage your risk. You may also have a higher risk of getting other cancers such as ovarian cancer, and your family may have a higher risk. Thats something you would talk with the genetic counselor about.
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Myth #: People With Metastatic Breast Cancer Look Sick And Lose Their Hair
You dont look sick. You look so well. Why do you still have your hair? Are you sure you have cancer? These are comments that people with MBC report hearing. But there are many treatment options besides chemotherapy, and people often appear well while taking them.
As NancyHB comments: Id much rather be a poster child for how sometimes we can live with, rather than die from, MBC at least for a while. Instead, I find myself defending against people who are increasingly becoming impatient with my lack of cancer-patient appearance. Im grateful for this time of feeling good, and theyre harshing my buzz.
Some people with MBC report that they actually look better than they feel while in treatment. So they sometimes have to let family and friends know that even though they appear fine, they dont feel well.
Shetland Pony notes: If she looks good, she is good. Nope. Many of us suffer from the invisible disability of fatigue. I would venture to say every available treatment causes us some level of fatigue. We struggle to keep up. It may look like we are doing the bare minimum when we are really giving it our all.
JoE777 of Texas adds: The new normals advertised about therapies on TV are deceiving about the side effects. They talk about side effects while women are skipping through life. not looking to show the harsh side effects but think there is something wrong with me that my life is not like that.
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How Life Expectancy And Relapse Differ From Positive Tumors
Questions about the survival rate and recurrence rate are very common when someone is diagnosed with triple-negative breast cancer . While prognosis is, on average, poorer than with hormone receptor or human epidermal growth factor receptor 2 positive tumors, triple-negative breast cancer is a very heterogeneous disease. On a positive note, and unlike hormone-positive tumors that commonly recur late , late recurrence is less common with triple-negative tumors. The recent approval of immunotherapy only for triple-negative disease is also optimistic.
We will look at factors that may affect survival or recurrence as well as the statistical rates of both. We will also look at life expectancy with stage 4 triple-negative breast cancers and recent case reports of a few long-time survivors.
Statistics Don’t Account For Late Recurrences
When comparing triple-negative breast cancer to positive tumors, it’s important to keep in mind late recurrences. Most statistics are presented as five-year survival rate, and in this setting, triple-negative breast cancer can look more ominous. But looking at longer periods of time, say 20 years following diagnosis, this may be different.
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Triple Negative Bc Bone Mets And What To Expect
After a hard battle in 2017/2018 with TNBC at 42 yrs of age-which resulted in chemo, mastectomy more chemo and radiation I thought that I had made it and had a wonderful year getting back to life with my beautiful children and amazing family and friends.;;
Then Nov 2019 I went for a routine check up mentioned minor back ache and after a MRI, CT Scan and PETScan was rediagnoised with Bone Mets in nearly in every bone. It had silently crepted around my bones.;;
Since November I have been treated with Immunotherapy and Chemotherapy with a mixed response.;;
I would be grateful to hear what treatment other people are on and how you are doing?;;
I have just got my head around it being incurable but it’s the not knowing when the pain will really start or what life needs to look like now? What decisions I make about work and what the outlook will be for;my children, family and friends.;;
Sorry for the long message and it would be lovely to speak with people who are in a similar position to understand what does tomorrow and the next day or month or year look like.;;
Wishing you all the best
Hi there Kar…
So so sorry your going through this heartbraking time at the moment,; it must feel so confusing, with a huge question mark …
Sending you a vertual hug…. Chrissie x
Hi kar
Welcome to the forum the club nobody wants to join.;
If i can help in any way please let me know.;
Billy;