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Triple Negative Breast Cancer Chemo

Immune Checkpoint Blockade With Monotherapy

Major Breakthrough In Treating Triple-Negative Breast Cancer

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.

Who Is Most At Risk For Triple

TNBC tends to be more common in women under 40 years old. Its also more common in African American women.

People who have a mutation in a gene called BRCA1 also have a higher TNBC risk. BRCA genes help repair DNA in our cells. If this gene is mutated, cells cant fix broken DNA. This can lead to breast cancer.

Whats more, up to 72% of women who have a BRCA1mutation will develop breast cancer by 70 to 80 years old.

What Are Breast Cancer Subtypes And Why Do They Matter

Your breast cancer subtype is one factor healthcare providers take into account when theyre deciding how to treat your cancer. Thats because not all cancer treatments are successful with all breast cancer subtypes.

Providers look at your cancer cells to identify subtypes. Specifically, they look for molecules on your cells surfaces. These molecules, called receptors, are built to order so only certain substances can climb on and start affecting what your cells do.

Breast cancer cells receptors are open to estrogen and progesterone. Understanding if your breast cancer cells have receptors and if theyre housing hormones helps providers determine how your breast cancer might spread and what treatment might be most effective.

The other type of breast cancer that has another receptor is called her-2 neu. This receptor makes the cells more active, but allows healthcare providers to treat the cancer with specific medicines that target her-2 proteins. If your breast cancer doesnt have her-2 neu and hormone receptors, its called triple negative.

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Treatment For Triple Negative Breast Cancer

The main treatments for triple negative breast cancer are surgery, chemotherapy and radiotherapy. The treatment you need depends on:

  • where the cancer is
  • the size of the cancer and whether it has spread
  • how abnormal the cells look under the microscope
  • your general health

You might have surgery to remove:

  • an area of the breast
  • the whole breast

When you have your surgery, the surgeon usually takes out some of the lymph nodes under your arm. They test these nodes to see if they contain cancer cells. The surgeon might check the lymph nodes closest to the breast using a procedure called sentinel lymph node biopsy. Testing the lymph nodes helps to find the stage of the cancer and decide on further treatment.

After breast conserving surgery you usually have radiotherapy to the rest of the breast tissue.

Risk Factors For Triple Negative Early Breast Cancer

Cancers

Anyone can get triple negative breast cancer, however there are some things that increase a persons risk.

Having an inherited BRCA mutation

Everyone has BRCA1 and BRCA2 genes. These genes normally prevent cancers from developing. However if there is a fault, called a mutation, in one of these genes, it can increase a persons risk of developing breast cancer and other cancers including ovarian cancer and prostate cancer in men. These gene mutations can be passed down through families.

About 5-10% of all people diagnosed with breast cancer have an inherited BRCA1 or BRCA2 gene mutation.

A BRCA1 mutation is associated with a higher risk for triple negative breast cancer. Not all breast cancers caused by BRCA mutations are triple negative, however, and not all triple negative breast cancers are caused by inherited BRCA mutations.

BRCA2 mutations are more likely to be present in oestrogen receptor positive breast cancer.

If you have a strong family history of breast and/or ovarian cancer , it is possible that you and your relatives could carry a BRCA mutation. For more information on breast cancer and family history, visit thebreast cancer in the family section of this website.

Being premenopausal

Premenopausal women have a higher rate of triple negative breast cancer than postmenopausal women. Scientists do not yet understand why this is the case, however research is currently underway in this area.

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Treatment For Triple Negative Early Breast Cancer

Treatment for triple negative early breast cancer may involve:

As triple negative breast cancer is usually very responsive to chemotherapy, your medical oncologist will most likely develop a chemotherapy treatment plan for you. This will take into account your own individual needs and preferences.

Chemotherapy for triple negative breast cancer is often given before surgery. This is called neoadjuvant chemotherapy. There are a number of benefits in having chemotherapy before surgery.

  • You can see if the chemotherapy is working .
  • You may be able to have breast conserving surgery instead of mastectomy if the tumour shrinks enough.
  • It gives you time to have genetic testing done to determine if you have an inherited gene mutation if the test comes back positive it may affect your decision around what type of surgery to have.

Treatment for triple negative breast cancer may also include radiotherapy after surgery, especially if you have breast conserving surgery.

You may be offered immunotherapy treatment through a clinical trial, although there are strict eligibility criteria. You can talk to your medical oncologist about any clinical trials that may be suitable for you.

Side Effects Of Targeted Treatments And Hormone Therapy

Targeted treatment drugs and hormone therapy dont have the same effect on the body as do chemotherapy drugs, but they can still cause side effects.

Side effects of certain targeted therapies can include diarrhea, liver problems , nerve damage, problems with blood clotting and wound healing, and high blood pressure.

The side effects of hormone therapy are dependent on the type of therapy and include hot flashes and joint pain .

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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.

Why Targeted Therapy Cant Be Used

Precision Medicine in Metastatic Triple Negative Breast Cancer

Targeted therapies take aim at cancer cells by interfering with the activity of receptors that fuel cancer growth. For example, tamoxifen and aromatase inhibitors target estrogen receptors. Herceptin targets HER2 receptors. These treatments are effectivebut only if a cancer tests positive for such receptors. As TBNC, by definition, is negative for them, the disease will not respond to targeted therapies.

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Possible Side Effects Of Chemo For Breast Cancer

Chemo drugs can cause side effects. These depend on the type and dose of drugs given, and the length of treatment. Some of the most common possible side effects include:

Chemo can also affect the blood-forming cells of the bone marrow, which can lead to:

  • Increased chance of infections
  • Easy bruising or bleeding

These side effects usually go away after treatment is finished. There are often ways to lessen these side effects. For example, drugs can be given to help prevent or reduce nausea and vomiting.

Other side effects are also possible. Some of these are more common with certain chemo drugs. Ask your cancer care team about the possible side effects of the specific drugs you are getting.

Platinum Agents: Are They Specific To Tnbc

The use of platinum agents for breast cancer has a long history dating to the early 1970âs and includes over 200 clinical trials in breast cancer patients. Platinum agents were initially tested in patients with advanced breast cancer, both as a single agent and in combination with other drugs, and were shown to be active when given early in the course of the disease. Platinum agents were not readily adopted, perhaps because of the superior therapeutic index of other drugs under development at the time, notably the taxanes. Small studies demonstrated objective response rates ranging from 42% to 54% with the use of cisplatin as a single agent, but response rates were lower in women who had received prior chemotherapy for metastatic disease.2628 When cisplatin was given after other chemotherapy, the response rate fell to 0-9%. 2933 Notably, these studies used cisplatin in patients regardless of ER, PR, and HER2 status. Several combination regimens were also explored, particularly cisplatin combined with taxanes, but there seemed little reason to continue these combinations when the taxanes were found to be highly active and relatively less toxic. 34

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How Does Egfr Contribute To The Fight Against Cancer

Epidermal growth factor receptor is a protein that is found in certain cells. This protein can bind to something called epidermal growth factor . When the two combine, the EGF stimulates cell division and growth. This has several benefits for the body for example, EGFR and EGF play an important role in wound healing.

EGFR is reportedly overexpressed in over three quarters of triple negative breast cancer cases. Scientists have therefore developed drugs that block EGFR proteins to prevent cells from growing too much

According to Dr. Joyce Schröder, head of the Department of Molecular and Cell Biology at the University of Arizona and senior author of this study, most triple-negative breast cancers expressed the EGFR, making it a potential target with great impact.

The drug developed by the research team prevents EGFR from reaching a part of the cell that keeps the cancer alive. The therapy is able to stop the EGFR protein in cancer cells, but not in healthy cells.

The therapy enters the cell and prevents EGFR from accumulating in the cell nucleus, explained Dr. Schröder. Nuclear EGFR is thought to drive aggressive, metastatic breast cancer, and by blocking NegFR, we hoped to develop a treatment for metastatic triple negative breast cancer.

The research team also stated that there are no unwanted side effects as their therapy leaves healthy cells alone.

New Medications For Metastatic Breast Cancer

SABCS2020: Chemo

Immunotherapy drugs called checkpoint inhibitors have led to a significant improvement in survival rates for lung cancer and melanoma.

In 2019, Tecentriq became the first immunotherapy drug to be approved for triple-negative breast cancer that is metastatic or locally advanced but unresectable . However, in August 2021, Tecentriq’s manufacturer voluntarily withdrew that indication in the United States.

However, also in 2021, the Food and Drug Administration approved Keytruda for high-risk, early-stage, triple-negative breast cancer. It is used in combination with chemotherapy as a neoadjuvant treatment , and then continued as a single agent as adjuvant treatment .

PARP inhibitors are another class of medication that may alter survival rates in the future, particularly among women who have hereditary breast cancer .

For bone metastases, bone-modifying drugs may be effective in both treating metastases and possibly reducing the development of further metastases in bone.

Finally, for people who have only a single or a few metastases , treating these metastases locally may be an option. While studies are young, treating oligometastases may improve survival or even lead to long-term survival for a minority of people.

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Update On Strategies To Improve Treatment For Triple Negative Breast Cancer

Approximately 12% of all breast cancers are TNBC, meaning that they are estrogen-receptor negative , progesterone-receptor negative , and human epidermal growth factor receptor 2-negative . This means that TNBC is not stimulated to grow from exposure to the female hormones estrogen or progesterone, nor through an overactive HER2 pathway.

Unfortunately, many available and effective treatment options for the majority of breast cancers block the growth stimulating effects of ER, PR and/or HER2 therefore, TNBC has had limited therapeutic options.

In addition, TNBC tends to be an aggressive type of cancer, is often diagnosed at a more advanced stage, and proportionately affects younger women more often than other breast cancers. Novel treatment options for TNBC have lagged behind that of other types of breast cancers.

The development of more effective treatment for triple negative breast cancer requires that new and innovative therapies be evaluated in TNBC patients. Areas of active investigation aimed at improving the treatment of TNBC include some of the following:

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Risk Factors For Triple

Doctors arenât sure what makes you more likely to get triple-negative breast cancer. Not many women do â it only affects up to 20% of those who have breast cancer. Youâre most at risk for triple-negative breast cancer if you:

  • Are African-American or Latina
  • Have what your doctor will call a BRCA mutation , especially the gene BRCA1

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Effects On Different Races And Ethnicities

In general, young women and Black women have a higher chance of being diagnosed with triple-negative breast cancer than older women and women of other races or ethnicities. The American Cancer Societyâs Breast Cancer Facts & Figures 2019-2020 reports that of all breast cancers diagnosed in Black women, about 21% are triple-negative. In comparison, only 10% of breast cancer diagnosed in non-Hispanic white women and Asian/Pacific Islanders is triple-negative, and only 12% of breast cancer diagnosed in American Indian/Alaska Native women and Hispanic women is triple-negative.

Though Black women have the highest chance of being diagnosed with triple-negative disease compared to women of other races, the rate of triple-negative diagnosis in Black women is still lower than diagnosis of other breast cancers. Like women from all racial and ethnic groups, Black women are most often diagnosed with hormone receptor-positive breast cancer. Of breast cancers diagnosed in Black women, 61% are hormone receptor-positive.

Home Remedies And Lifestyle

Chemotherapy Options for Triple Negative Breast Cancer

If you have had any of the standard therapies for TNBC, you may experience symptoms due to your cancer or as side effects of treatment.

There are a number of strategies you can use at home to alleviate your symptoms:

  • Ice packs: Some women experience pain or swelling after breast cancer surgery or due to radiation. Ice packs, when used carefully, can help.
  • Massage: You may have pain, aches, or soreness. If approved by your doctor, using a massaging device may be soothing.
  • Exercise: Often, exercise can help reduce the swelling that follows a mastectomy or an axillary dissection. If swelling is a persistent problem for you, talk to your doctor about starting some regular exercises that you can do on your own. Often, keeping your arm lifted while it is resting is also recommended.
  • Armband: For some women, a snug wrap around the hand or arm can help reduce the swelling that occurs after breast cancer surgery.
  • Diet: You can experience a loss of appetite due or nausea to chemotherapy. And sometimes, TNBC can be so aggressive that it causes malnourishment and weight loss. You may need to work with a dietitian to make sure that you are getting a healthy balance of nutrients.
  • Fluids: Drinking fluids such as water, ginger ale, or electrolyte drinks can help replenish you when mild dehydration is a problem . Ginger ale also counteracts mild nausea.

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Targeted Therapy For Her2

In about 1 in 5 women with breast cancer, the cancer cells have too much of a growth-promoting protein known as HER2 on their surface. These cancers, known as HER2-positive breastcancers, tend to grow and spread more aggressively. Different types of drugs have been developed that target the HER2 protein.

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Managing Residual Disease Following Neoadjuvant Chemotherapy

Although attaining pCR is the goal of neoadjuvant therapy, optimal management of those who do not meet this end point is critical as these patients have a relapse risk that is six to nine times higher than that of patients achieving pCR6,7.

The CREATE-X clinical trial showed that six to eight cycles of adjuvant capecitabine improved DFS and OS in the TNBC cohort. DFS rates were 69.8% in the capecitabine arm and 56.1% in the control arm , and OS rates were 78.8% and 70.3% 46. The importance of targeting adjuvant capecitabine to those with residual disease was recently highlighted by the results of the phase 3 GEICAM/CIBOMA trial. This randomised phase 3 trial of 876 patients who had early-stage TNBC and who had completed standard adjuvant or neoadjuvant polychemotherapy was designed to analyse the impact of adjuvant capecitabine for all patients with TNBC regardless of their pCR status. There was no significant difference in 5-year DFS and OS between the treatment groups, highlighting the need to choose a treatment-resistant group47. The results of the CREATE-X trial now compel most clinicians to treat early-stage TNBC with neoadjuvant chemotherapy in order to understand who should have capecitabine. Whilst capecitabine should be considered, ongoing trials are evaluating new agents for TNBC with residual disease after neoadjuvant chemotherapy.

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