Advances In Breast Cancer Research
A polyploid giant cancer cell from triple-negative breast cancer.
NCI-funded researchers are working to advance our understanding of how to prevent, detect, and treat breast cancer. They are also looking at how to address disparities and improve quality of life for survivors of the disease.
This page highlights some of the latest research in breast cancer, including clinical advances that may soon translate into improved care, NCI-supported programs that are fueling progress, and research findings from recent studies.
The Flip Side Of The Coin: Immune
The price of improving patients outcomes with the addition of immunotherapy is the risk of irAEs beyond the toxicities of traditional chemotherapy. The most common irAEs observed in KEYNOTE-522 were infusion reactions , thyroid impairment , skin toxicities , pneumonitis , hypophysitis , colitis and hepatitis in combined neoadjuvant and adjuvant phases. Importantly, some of these are expected to be irreversible, permanently conditioning the quality of life of patients in this curable setting. Additionally, concern on the impact of immunotherapy on fertility exist, particularly since TNBC often occurs in pre-menopausal patients. In this regards, appropriate training of clinicians in the early identification and management of irAEs will be key for the mitigation of immunotherapy side effects. Concomitantly, these risks should be discussed with patients upfront, to provide a clear overview of the risks/benefits balance of adding immunotherapy to chemotherapy for the treatment of their tumor.
A Key Instrument In Precision Medicine
The University of Kansas Cancer Center deputy director and The University of Kansas Medical Center director of molecular oncology Andrew Godwin, PhD, has worked closely with Sharma on developing this registry, which helps support the movement toward precision medicine, an approach that customizes treatment based on an individuals genes, environment and lifestyle.
The information gleaned from these patients can be used to establish new therapeutic approaches for sub-populations of triple-negative breast cancer patients and help us better predict how a specific patient may respond to a given therapy. Our goal in precision medicine is to expand this type of approach to other diseases so we can provide the best possible care to patients in our region, Godwin says.
The first published finding to come out of the registry involved testing the prevalence of the BRCA1 and BRCA2 mutation in patients. Women with this mutation have a risk of breast cancer that is about 5 times the normal risk. Researchers found that 15% of triple-negative patients have this mutation.
This finding demonstrates that testing may better predict chances of developing triple-negative breast cancer. This has the potential to alter genetic testing guidelines, including its coverage by insurance, Sharma notes.
Every finding from this registry leads to a better understanding, which will hopefully lead to improved treatment, Sharma says.
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Tnbc Targeted Therapy And Potential Treatment Regimens
Due to the high heterogeneity of TNBC, it is particularly difficult to discover new therapeutic targets and perform targeted therapy. Currently, there are a large number of ongoing clinical trials targeting specific receptors or on targeted therapies of TNBC based on immunohistochemical staining results.
What Questions Should I Ask My Doctor
You will have lots of questions about your cancer, starting with your diagnosis. Here are some basic questions you might ask:
- What is triple negative breast cancer?
- How do you know my cancer is triple negative breast cancer?
- Why did I get this cancer?
- Do I need genetic testing?
- Has my breast cancer spread, and if so, how far has it spread?
- What is the stage of my cancer?
- What is my prognosis or expected outcome?
- What treatments do you recommend?
- Why do you recommend those treatments?
- What are those treatment side effects?
- Will I need surgery? If so, what surgery do you recommend and why?
- Im interested in participating in clinical trials. Are you able to help me find one?
- Do you know if there are any local support groups?
A note from Cleveland Clinic
Triple negative breast cancer is one of the more challenging breast cancers to treat. You might be discouraged by what you have read about triple negative breast cancer. But there are a number of very effective treatments for triple negative breast cancer, including immunotherapy, chemotherapy, surgery and radiation. And every day researchers learn more about this rare cancer. Their knowledge is your power. If youre concerned you arent getting the straight story about your cancer, ask your healthcare provider to walk you through your diagnosis and treatment options.
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Who Is Most Likely To Have Tnbc
Triple negative breast cancer appears more frequently in women age 40 and younger than in older women. Black and Latina women are more likely to develop TNBC than white women. Women who have the gene change BRCA1 are more likely to develop TNBC than other women. When the BRCA1 gene mutates, it stops preventing cancer and appears to make your bodys cells more vulnerable to cancer.
What This Means For You
If youve been diagnosed with triple-negative breast cancer, this study offers some encouraging and interesting information. The results strongly suggest that triple-negative breast cancers are not all the same and that certain subtypes have better survival rates than hormone-receptor-positive breast cancer.
Determining the subtype of triple-negative breast cancer is not universally done. Still, many cancer centers do this type of testing. You may want to ask your doctor about this study, as well as whether subtype testing has been done as part of your pathology report and what it means for your prognosis and treatment.
Armed with the most complete information you can get, you and your doctor can make the best decisions for your unique situation.
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Diagnosing Triple Negative Breast Cancer
In many women the cancer is found during breast screening. But symptoms such as a breast lump can be a sign of breast cancer. So it is important to get any symptoms checked by your doctor.
If you have symptoms and see your GP they refer you to a specialist breast clinic. At the breast clinic the doctor or breast care nurse takes your medical history and examines your breasts. They also feel for any swollen lymph nodes under your arms and at the base of your neck.
You have some of the following tests:
- a biopsy your doctor or nurse take a small sample of cells or tissue from your breast to look at under a microscope
Depending on your age and whether other family members have had breast cancer, your doctor might refer you for gene testing. This is to find out if there is a fault in the BRCA cancer gene.
What Are Symptoms Of Triple Negative Breast Cancer
TNBC symptoms are the same as other common breast cancers. And many breast cancer symptoms are similar to other less serious conditions. That means having certain symptom doesnt mean you have breast cancer. Possible breast cancer symptoms include:
- A new lump or mass.
- Swelling in all or part of a breast.
- Nipple retraction, when your nipple turns inward.
- Nipple or breast skin thats dry, flaking, thickened or red.
- Nipple discharge that is not breast milk.
- Swollen lymph nodes. This symptom happens when breast cancer spreads to the lymph nodes under your arm or near your collarbone.
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When Should I Go To The Emergency Room
You might also have unusually strong side effects from your cancer treatment. While your healthcare provider likely gave you medication to help control your side effects, you should go to the emergency room if your side effects continue despite medication.
Many cancer treatments affect your immune system, increasing the chance you will develop infections. Symptoms that might require an emergency room visit during treatment are:
- Fever of 100.5 and above.
- Persistent nausea and vomiting.
Src Tyrosine Kinase Inhibitors
The Src tyrosine kinase is also over-expressed in breast cancer and is associated with metastatic disease progression . Dasatinib is an oral, small-molecule tyrosine kinase inhibitor that acts on proteins src and abl. Preclinical studies show dasatinibs activity to inhibit the growth of basal-like breast cancer cell lines , providing the rationale for clinical research in this specific subgroup. A phase II trial showed a clinical benefit rate of 9% in TN metastatic breast cancer, but discontinuation of therapy and dose reductions weakened the results . There are currently several studies evaluating dasatinib as monotherapy or in combination regimens in this setting.
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Heat Shock Protein 90 Inhibitors
Heat shock protein 90 is a cellular chaperone protein that facilitates the post-translational maturation and stabilization of a number of conformationally labile client proteins, including steroid receptors, RAF-1, cyclin-dependent kinase 4, AKT and other proteins that play a role in transducing proliferative signals . When heat shock protein 90 function is inhibited, their client protein is degraded by proteosomes.
Geldanamicyn and tanespimycin have demonstrated activity in HER2-positive metastatic breast cancer disease . The inhibitor PU-H71 demonstrated impressive response in TN breast cancer disease in preclinical studies .
What Is The Risk For Triple
The disease can affect anyone, but is more likely to show up in those who are:
- Younger than age 50 .
- Black or Latinx.
- Living with a genetic condition called BRCA mutation that increases the risk for breast cancer and other forms of cancer. Most cancers diagnosed in people with the BRCA1 mutation are triple negative.
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A New Treatment Option Is Now Available
On March 11, 2022, the Food and Drug Administration approved a drug called Olaparib to treat HER2-negative, high-risk early breast cancer. Data from a phase 3 clinical trial of 1,836 patients, of which about 82% had the triple-negative disease, led to the approval. The clinical trial results demonstrated that Olaparib reduced the risk of death by 32%, compared to the placebo. The recent FDA approval brings new hopes to patients with early triple-negative breast cancer since many currently available therapies couldnt effectively control the progression of their cancers.
What Is The Prognosis For Triple
A good treatment result depends on several factors. Chemotherapy is what can really make a difference in the outcome. The size of the invasive part of the tumor, and the number of involved lymph nodes can also greatly influence your prognosis, Sun says, but adds that if the cancer has spread , the prognosis is less certain.
There is hope, even with this serious diagnosis, and staying optimistic is essential. It can be stressful and scary to go through chemo, but positive thinking can make a difference. You have to believe that its doing you good, and for most people, it does.
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Prognosis And Survival Rates
Treatment may make triple-negative breast cancer go away. It depends on the size of your tumor, how quickly your cancer grows, and whether the cancer has spread to the lymph nodes or other parts of your body. The treatments may cause side effects like nausea, vomiting, pain, fatigue, or mental fuzziness .
Itâs hard to say exactly what the odds are because cancer affects everyone differently. Plus, how well you do depends on how early you catch the cancer and how well you responded to treatment.
In general, about 91% of all women with triple-negative breast cancer are still alive 5 years after diagnosis. If the cancer has spread to the lymph nodes near the breast the 5 year relative survival rate is about 65%. If the cancer has spread to distant places, the 5 year relative survival rate is 12%.
Trials For Advanced Triple Negative Breast Cancer
Trials are comparing different types of chemotherapy to see which are better at treating advanced disease. For example, researchers are waiting for the results of the Triple Negative Trial to find out whether it is better to use carboplatin or docetaxel.
Research is looking at using targeted cancer drugs alongside other treatments. For example, a trial is using a drug called atezolizumab in combination with chemotherapy. Some trials are testing a drug called pembrolizumab. Researchers think that these targeted drugs on their own might help to control the growth of the cancer.
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Where Do These Numbers Come From
The American Cancer Society relies on information from the Surveillance, Epidemiology, and End Results Program database, maintained by the National Cancer Institute , to provide survival statistics for different types of cancer.
The SEER database tracks 5-year relative survival rates for breast cancer in the United States, based on how far the cancer has spread. The SEER database, however, does not group cancers by AJCC TNM stages . Instead, it groups cancers into localized, regional, and distant stages:
- Localized: There is no sign that the cancer has spread outside of the breast.
- Regional: The cancer has spread outside the breast to nearby structures or lymph nodes.
- Distant: The cancer has spread to distant parts of the body such as the lungs, liver, or bones.
How Were Endingbreast Cancer
Every year in the U.S., approximately 235,000 men and women arediagnosed with breastcancer and more than 40,000 succumb to it. Nearly 69,000 patientshave the subtype known as triple-negative breast cancer , whichcauses almost 12,000 deaths annually. The Breast Cancer MoonShot® is determined to defeat this deadly type of breast cancer.
A flood of new knowledge and technology makes now the time tofast-track the cancer fight and make a giant leap for patients. We’remerging todays high potential for achievement with our uniqueknowledge and expertise, derived from decades of leadership in thecancer field.
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What Is Triple Negative Breast Cancer
Triple negative breast cancers are cancers whose cells dont have receptors for:
- the hormones oestrogen and progesterone
- a protein called Her2
Your doctor uses a sample of your cancer to test the cells for these receptors. You might have this test following a biopsy of the cancer, or after surgery to remove it.
A rare type of breast cancer known as basal type breast cancer is usually triple negative. Some women with triple negative breast cancer also have a BRCA1 gene fault. BRCA1 is one of the gene faults that can increase the risk of breast cancer within families.
Some men have triple negative breast cancer but this is very rare. Most men have oestrogen receptors in their cancer cells.
What You Need To Know
- Triple-negative breast cancer accounts for about 10% to 20% of all breast cancer cases.
- Every cancer diagnosis is unique, but in general, triple-negative breast cancer is a more aggressive type of tumor with a faster growth rate, higher risk of metastasis and recurrence risk. Therefore, it often requires chemotherapy as part of the treatment.
- Surgery is also an important part of treatment, but if a tumor is small and localized, mastectomy may not be necessary. Chemotherapy can shrink triple-negative breast tumors, and patients can become candidates for less-extensive surgery.
- Triple-negative cancers are more common in patients with hereditary genetic mutations, and genetic counseling and testing should be considered.
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How Is Triple
Once a breast cancer diagnosis has been made using imaging tests and a biopsy, the cancer cells will be checked for certain proteins. If the cells do not have estrogen or progesterone receptors , and also do not make any or too much of the HER2 protein, the cancer is considered to be triple-negative breast cancer.
What Is A 5
A relative survival rate compares women with the same type and stage of breast cancer to women in the overall population. For example, if the 5-year relative survival rate for a specific stage of breast cancer is 90%, it means that women who have that cancer are, on average, about 90% as likely as women who dont have that cancer to live for at least 5 years after being diagnosed.
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Study Finds Nanomedicine Targeting Lymph Nodes Key To Triple Negative Breast Cancer Treatment
In mice, nanomedicine can remodel the immune microenvironment in lymph node and tumor tissue for long-term remission and lung tumor elimination in this form of metastasized breast cancer.
Research from the University of Michigan Rogel Cancer Center could provide a new approach to treating an aggressive form of breast cancer.
A study led by Duxin Sun, Ph.D., found that targeting the immune microenvironment in lymph nodes and tumors simultaneously led to long-term tumor remission in mice models of metastatic triple negative breast cancer. Further, using nanoparticles to deliver these immune-altering drugs increases treatment efficacy. These results appear in Science Translational Medicine.
Immunotherapy combined with chemotherapy has been long approved as standard treatment option for triple negative breast cancer but only shows a limited response in patients. Many believe that the tumor immunosuppressive microenvironment is one of the main contributing factors for the poor responses in those with TNBC.
Sun,Charles R. Walgreen Jr. Professor of Pharmacy and Professor of Pharmaceutical Sciences at the U-M College of Pharmacy, says that previously developed immunomodulators work well in animal models, but fail in clinical trials. He and his team wanted to come up with a better approach that would treat TNBC patients long-term that could withstand the rigor of clinical trials. To do this, they had to look beyond just the tumor microenvironment to the lymph nodes.
Treating Triple Negative Breast Cancer
Triple negative breast cancer can be treated with a combination of
Research has shown chemotherapy generally has a larger benefit for triple negative breast cancer compared to oestrogen receptor positive breast cancer. Chemotherapy for triple negative breast cancer is often given before surgery. The drugs used are likely to include carboplatin or cisplatin.
Some breast cancer treatments, such as hormone therapy and HER2 targeted therapies are of no benefit to people with triple negative breast cancer.
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