Sunday, March 3, 2024

Triple-negative Breast Cancer Treatment 2020

Current Landscape Of Personalized Clinical Treatments For Triple

2020 PEA Program Metastatic Triple-Negative Breast Cancer Immunotherapy Options & Side Effects
  • 1Department of Thyroid and Breast Surgery, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, China
  • 2Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 3Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 4Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

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.

New Treatments Needed For Advanced Triple

Triple-negative breast cancer tends to be more aggressive, harder to treat, and more likely to recur than other forms of the disease, such as hormone receptorpositive or HER2-positive breast cancers.

Conventional chemotherapy drugs have not been effective against triple-negative breast cancer, and new treatment options are needed, said Jung-Min Lee, M.D., of the Womens Malignancies Branch in NCIs Center for Cancer Research.

In the KEYNOTE-355 trial, 847 patients with advanced triple-negative breast cancer were randomly assigned to receive chemotherapy plus placebo or chemotherapy plus pembrolizumab.

The study assessed the amount of time before the disease worsened and overall survival in all patients, in those with PD-L1 combined positive scores of 1 or more, and in those with combined positive scores of 10 or more. The trial was funded by Merck, the manufacturer of pembrolizumab.

The PD-L1 combined positive score is essentially a measure of the extent to which cells in a tumor produce PD-L1, the immune checkpoint protein that pembrolizumab targets. By blocking immune checkpoints, pembrolizumab and other immune checkpoint inhibitors unleash the immune system against cancer cells.

The incidence of treatment-related side effects, including serious side effects, was similar between the two groups of patients in the study.

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Early Stage Clinical Trials

In a proof of concept study published in the Lancet, authors investigated olaparib in patients with advanced metastatic breast cancer with germline BRCA1/BRCA2 mutations. They investigated two doses of olaparib at 400 mg BD and 100 mg BD. Approximately half of patients in this study had TNBC with the remainder having other histological subtypes. Patients were heavily pretreated with a median of 3 prior chemotherapy regimens and platinum sensitivity was not needed for trial enrolment. Overall response rates were impressive in this heavily pre-treated population at 41% in the group receiving the higher dose and 22% in the group receiving the lower dose.

Kaufman et al investigated olaparib further in a large phase 2 basket trial with 298 patients in a single-arm study. Patients with any advanced solid-organ malignancy were included if they harboured a gBRCA mutation. In the breast cohort, patients may have received multiple lines of treatment and there was no requirement for platinum sensitivity. Response rates were modest with only 8 of 62 patients responding in this unselected population.

Isotope Incorporation Into Co

Merck

Zirconium-89 oxalate was obtained from DC AMS Pharma , which was produced via 89Y89Zr reaction with a specific activity of 352.2±26.4 MBq/g of Zr . Zirconium-89 chloride was obtained from 89Zr-oxalate after the heat vaporization of oxalate by the addition of concentrated HCl. During the UiO-67 nMOF synthesis, 148 MBq of 89ZrCl4 was added into a 2-mL reaction mixture while the same reaction condition was maintained for UiO-67. After obtaining the 89Zr-incorporated UiO-67, cobalt embedding, Py-PAA-PEG-Mal functionalization and F3 conjugation was also carried out for in vitro and in vivo evaluation of 89Zr-Co-UiO-67 conjugates.

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What Can Your Pathology Report Tell You About Tnbc

The analysis of your tissue sample from a biopsy or surgery will indicate that your tumour does not express an oestrogen receptor , progesterone receptor or human epidermal growth factor 2 . In your pathology results, you may read about the percentage of cells being positive for oestrogen and progesterone. If this percentage is less than 1%, the cancer is considered to be hormone receptor negative. For the HER2 protein, the result would be rated as 0, 1+ or 2+ to be considered HER2-negative18.

Triple negative cancer cells tend to look very different from normal breast cancer cells, which means that the cancer is classified as high grade . Cells that behave in this way tend to have high levels of markers that indicate cell proliferation such as Ki67, p53+ and p63+. This means that the cells grow and divide quickly 19.

Want to keep track of all the information from your pathology report? With the OWise breast cancer app you can input your details and the app will generate a personalised treatment report based on your breast cancer subtype!

To better understand your pathology results, head to our previous pathology report blog.

Immune Checkpoint Blockade With Monotherapy

As noted on clinicaltrials.gov , approximately half of the registered studies are focused on immune checkpoint blocking-related therapies. Of these, greater than 100 clinical studies have already entered phase II or phase III, implying that immunotherapy is an important trend in TNBC treatment. Previous trials have shown positive results with pembrolizumab or atezolizumab monotherapy in TNBC. In the KEYNOTE-012 trial , 27 PD-L1-positive TNBC patients exhibited an ORR of 18.5%, and the median time to response was 17.9 weeks . Another targeting PD-L1 mAb, atezolizumab, was also reported to be safe and clinically active in mTNBC. In this phase I study , the evaluation of PD-L1 expression levels demonstrated an improved ORR, a longer OS, and a higher disease control rate in patients with at least 1% TILs expressing PD-L1. Interestingly, patients receiving first-line atezolizumab therapy exhibited a better prognosis , suggesting the superiority of atezolizumab combined with first-line.

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Symptoms Of Triple Negative Breast Cancer

The symptoms of triple negative breast cancer are similar to other breast cancer types.

Symptoms can include:

  • a new lump or thickening in your breast or armpit
  • a change in size, shape or feel of your breast
  • skin changes in the breast such as puckering, dimpling, a rash or redness of the skin
  • fluid leaking from the nipple in a woman who isnt pregnant or breast feeding
  • changes in the position of nipple

Make an appointment to see your GP if you notice anything different or unusual about the look and feel of your breasts.

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Keep in mind that survival rates are estimates and are often based on previous outcomes of large numbers of people who had a specific cancer, but they cant predict what will happen in any particular persons case. These statistics can be confusing and may lead you to have more questions. Talk with your doctor about how these numbers may apply to you, as he or she is familiar with your situation.

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Receptor Tyrosine Kinases Family

RTKs family is a kind of transmembrane enzyme-linked receptor on cell surface, composing of an extracellular ligand-binding region, a single transmembrane helix, a protein tyrosine kinase domain and juxta membrane regulatory regions . There are 58 different kinds of receptors, such as epidermal growth factor receptor , vascular endothelial growth factor receptor , insulin-like growth factor receptor , fibroblast growth factor receptor and AXL . RTKs binding to ligands to induce the dimerization of the receptors, which then activates the downstream PI3K/AKT/mTOR pathway, RTK/Ras/MAPK pathway and janus kinase/signal transducer and activator of transcription protein family pathway . The conduction processes are showed in Fig. 1. Mutations or disorders of different RTK can drive cancer progression, therefore, it is theoretical plausible to target these RTKs for cancer treatment . Now more and more tyrosine kinase inhibitors and anti-TKI antibodies have received approvement from U.S. Food and Drug Administration for applications in cancer treatment .

Fig. 1

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.

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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.

Molecular Heterogeneity Of Triple

Triple Negative Breast Cancer 2020 Year In Review

TNBC is the subtype with the worst prognosis due to its very high tumor heterogeneity, drug resistance, and the long-term lack of effective treatment other than chemotherapy . In terms of histological classification, about 95% of TNBC cases are histologically defined as non-specific invasive BC or invasive ductal carcinoma accompanied by no specific histological features . Compared with other BC subtypes, TNBC is more often related to genetic conditions. The histopathological features of TNBC may be caused by different genes and proteins, which provides a theoretical basis for the different pathological features of TNBC at different stages and different levels .

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Neoadjuvant And Adjuvant Settings

A PARP inhibitor appears to have efficacy for neoadjuvant treatment of patients with gBRCAm TNBC. Talazoparib achieved encouraging pCR in patients with gBRCAm breast cancer, including TNBC, and HR+ breast cancer, as a neoadjuvant single-agent without the addition of chemotherapy . Currently a larger, multi-center, neoadjuvant Phase II trial is ongoing. However, the addition of a PARP inhibitor to standard neoadjuvant chemotherapy was found to be not beneficial. In the BrighTNess Phase III trial the addition of PARP inhibitor veliparib to carboplatin and paclitaxel followed by doxorubicin and cyclophosphamide did not improve pCR whereas the addition of veliparib and carboplatin to paclitaxel did. Therefore, the addition of carboplatin but not veliparib to paclitaxel was proposed as a potential component of neoadjuvant chemotherapy for patients with high-risk TNBC .

PARP inhibitors have also been studied as an adjuvant single-agent therapy. The OlympiA Phase III trial was designed to assess olaparib in patients with gBRCAm and high-risk HER2-negative breast cancer who completed definitive local treatment and neoadjuvant or adjuvant chemotherapy. The primary outcome measure will be invasive DFS with a time frame of up to 10 years.

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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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What Are The Three Receptors In Breast Cancer

Triple-negative breast cancer: 5 things you should know. When doctors diagnose breast cancer, they look for three types of receptors estrogen receptor , progesterone receptor and human epidermal growth factor receptor 2 expressed in the breast cancer. These are what cause most breast cancers to grow.

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Treating Tnbc Vs Other Breast Cancers

2020 PEA Program Metastatic Triple-Neg Breast CancerTargeted Therapy Treatments & Side Effects

With other types of breast cancer, receptor status helps your doctor determine the most effective treatment. Each receptor has one or more targeted treatments that help destroy breast cancer cells and reduce the risk of the cancer returning. But TNBC doesnt have receptors to attack, so there arent any targeted therapies.

According to experts at Susan G. Komen, about 70 to 80% of breast cancers are hormone receptor-positive, meaning they can be treated with hormone therapy that either lowers estrogen production or blocks estrogen receptors. Since TNBC is hormone receptor-negative, hormone therapy isnt an effective treatment option. For the same reason, TNBC doesnt benefit from therapies aimed at attacking the HER2 protein.

TNBC has a poorer short-term prognosis than other types of breast cancer. In people with early-stage TNBC, 50% see their breast cancer return and 37% die in the first five years after surgery, according to a report in the Journal of Oncology Practice. After five years, the difference in breast cancer recurrence between hormone receptor-negative and hormone receptor-positive tumors decreases and eventually evens out, according to Susan G. Komen. This is because TNBC can be successfully treated.

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Phase Iii Embrca Trial

In the pivotal phase 3 study EMBRCA, authors investigated talazoparib in 431 patients with gBRCA mutations and MBC. Approximately half of patients had TNBC with the remainder having ER/PR-positive breast cancer. Patients had a median of 2 prior lines of chemotherapy and were randomised in a 2:1 manner to receive talazoparib vs physicians choice . Median PFS was greater in the talazoparib group compared to the control group-8.6 mo vs 5.6 mo with an objective response rate of 62.6% vs 27.2%. Benefit within the TNBC and HR positive subgroups was equivalent. Crucially however, median OS was not significantly greater in the talazoparib group compared to the placebo group . Patients in the talazoparib group did however have improved health related quality of life outcomes. More than a quarter of patients suffered from a grade 3 or grade 4 adverse event in the talazoparib group which was similar to the control group . Notably, one patient suffered from the rare but well described PARPi toxicity of acute myeloid leukaemia.

What Is The Treatment For Triple Negative Breast Cancer

Healthcare providers and researchers are making significant progress on TNBC treatments. Recent clinical trials are testing new combinations of drugs and new approaches to existing treatments. Some existing treatments are:

  • Chemotherapy: Providers might combine chemotherapy and surgery, with chemotherapy being used to shrink your tumor before surgery or after surgery to kill cancer cells throughout your body.
  • Surgery: This could be a lumpectomy to remove an individual lump, or a mastectomy to remove an entire breast. Providers then perform a sentinel node biopsy or axillary node surgery to look for signs your breast cancer has spread to your lymph nodes.
  • Radiation therapy: Post-surgery radiation therapy helps reduce the chances your cancer will return or recur.
  • Immunotherapy: This treatment stimulates your immune system to produce more cancer-fighting cells or help healthy cells identify and attack cancer cells. Immunotherapy can be added to chemotherapy to before surgery to shrink the tumor. You might also receive immunotherapy for about a year after your surgery and post-surgery radiation therapy.

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Sample Type And Sample Size Required

The minimum sample size required was calculated before data collection for the primary objective with the following assumptions: statistical significance level p< 0.05, targeted statistical power of 80%, eight prognostic factors , and minimum partial coefficient of determination considered clinically relevant R20.10. Under these assumptions, a sample size of 144 patients was finally required. Given the retrospective nature of the study, we expected that 15% of patients would have missing data on the primary outcome and at least one of the eight prognostic factors. Therefore, we decided to increase the number of enrolled patients to 170.

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Issues With Current Treatments

#VisualAbstract: Pembrolizumab plus chemotherapy improves survival in ...

According to Dr. Crystal Fancher, the lack of receptors to target mean that some treatments for other forms of breast cancer are not effective for triple-negative breast cancer.

Dr. Fancher is a surgical breast oncologist at the Margie Petersen Breast Center at Providence Saint Johns Health Center and an assistant professor of surgery at Saint Johns Cancer Institute, both in Santa Monica, CA.

Unlike other breast cancers that have hormone receptors, like HER2, triple-negative is harder to treat, she told MNT.

Dr. Jacoub explained that peoples outcomes tend to improve when they use chemotherapy in combination with other treatments. A course of treatment now typically includes immunotherapeutics, which we use before and after surgery as well as during a recurrence, he added.

Platinum chemotherapy, or chemotherapy using platinum-based drugs, is common in the treatment of triple-negative breast cancer due to its effectiveness. However, research has shown that severe side effects can limit its use.

One found around 40 specific side effects, including a decrease in bone marrow production, problems with kidney function, headaches, and other negative effects on the nervous system. There are some treatments available to address these side effects.

Dr. Nan estimated that about 40% of people can use a combination of immunotherapy and chemotherapy.

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