Triple Negative Breast Cancer

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What is Triple Negative Breast Cancer?

Triple Negative Breast Cancer (TNBC) is a type of breast cancer that is diagnosed in two U.S. women every hour, adding up to over 17,000 US women per year. TNBC develops in the breast because of the presence of abnormal or cancer cells that look and behave differently from the normal cells in the breast. TBNC can occur in women at any age, race or ethnicity. TNBC is more common in women of African, African-American, Caribbean, and Hispanic descent, as well as in pre-menopausal women, and women with BRCA1 mutations. Triple negative breast cancer also disproportionately affects young women and women of color.

TNBC is “triple negative” because these cancer cells lack 3 types of proteins that are known to help other cancer cells grow. These proteins are called receptors, and they are usually located on the surface of or inside of cells: estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth fact receptor 2 (HER2). There are several drugs that are targeted to block ER, PR and HER2 so that the cancer cells won’t grow. Since TNBC cells do not have any of the receptors, these types of treatment do not work. However, if caught early, TNBC can often be treated successfully with the common treatments of chemotherapy, radiation and/or surgery.

Researchers are continuing to learn more about TNBC. It is known that 10-20% of breast cancers are TNBC, and that there are 6 subtypes of TNBC. These subtypes are basal-like 1, basal-like 2, mesenchymal-like, mesenchymal stem-like, immunomodulatory and luminal androgen-receptor expressing. TNBC tends to grow faster than other types of breast cancer, and patients with TNBC have 16% percent less chance of surviving for 5 years after diagnosis, when compared to other types of breast cancer. Furthermore, TNBC tends to occur more commonly in women under 40 years old, and in African American and Hispanic women. But, it is not currently known what puts certain people at risk for developing TNBC. As we learn more about how TNBC behaves, we will be able to develop targeted drugs to cure this disease. Among the new treatments that are being developed and tested to treat TNBC, poly ADP-ribose polymerase (PARP) inhibitors, are showing promise. These are drugs that block PARP, an enzyme that cells use to repair damaged DNA.

Symptoms and Diagnosis

The symptoms of TNBC are similar to the other types of breast cancer. These include a lump in the breast, dimpling or other changes in the breast, a large or hard lymph node under your arm or near the clavicle, a nipple that turns inwards, and discharge from the nipple.

For your diagnosis, your doctor will describe the breast cancer in 3 ways:

  • Stage: This covers the size of the tumor (the group of cancer cells) and how much it has spread to other parts of your body. The stages rank from 0 to IV, with the higher stage representing more advanced cancer.
  • Grade: This tells how much difference there is between normal cells and the cancer cells. A higher grade means that the cancer cells look very abnormal, and that they are fast-growing.
  • Receptor Status: This tells if the tumor has receptors that are known to help cancer cells grow. For each receptor, it is present, it is “receptor positive” and if absent, it is “receptor negative.”

Prognosis

When thinking about TNBC, one of the most common questions is about prognosis – the expected outcome or course of the disease, and the likelihood of recovery. Some characteristics make the cancer more aggressive than others, leading to a poorer prognosis. However, many TNBC cases are treated successfully.

Prevalence

Of the estimated 1 million patients worldwide who are diagnosed annually with breast cancer, approximately 170,000 have TNBC.

The prevalence of TNBC is highest in premenopausal African American. Among all African American premenopausal women with breast cancer, 39% have TNBC. The prevalence of TNBC in non-African American women is 15%. Further, after adjusting for age and stage at diagnosis, African American women were almost 3-fold more likely than white women to have TNBC.

Risk Factors

It is currently unknown why some women are more likely to develop TNBC. However, there is an association between developing TNBC and age, ethnicity and gene mutations. Being in one or more of these risk categories does not mean that you will get TNBC, as the overall risk is still small.

  • Young women have a higher risk of being diagnosed with TNBC, whereas other breast cancer types typically occur in older women.
  • African American and Hispanic women are the most common ethnic groups who are diagnosed with TNBC. In particular, premenopausal African American women have a much higher risk of being diagnosed with TNBC than white women. Some studies suggest that this difference may be due in part to lifestyle. The risk of developing TNBC may be higher in women with lower rates of breastfeeding, women with high fertility and women with excess weight in the abdomen area – these characteristics are typically higher in African American women compared to other women.
  • People with a BRCA1 and BRCA2 gene mutations have a high risk of developing breast cancer, and if it occurs before age 50, it is usually TNBC. In fact, most BRCA1-related breast cancers and some BRCA2-related breast cancers are triple negative.

In addition, while women who have at least one child have a lower risk of breast cancer, women with TNBC may not have the protective benefit of childbearing. In other studies, being overweight has been shown to be associated with an increase in the risk of both premenopausal and postmenopausal TNBC.

Recurrence

TNBC are more likely to recur than other types of breast cancer. TNBC tend to occur within a few years, and when they recur, the prognosis is usually poor. Recurrence of TNBC often involves metastasis, typically spreading from the breast to the brain or lungs.

Survival

Among women with TNBC, 77% have survived for at least 5 years. In comparison, 93% of women with other types of breast cancer survived for at least 5 years. It is also important to note that women with TNBC have a higher risk of death within 5 years of diagnosis, but not after that time period. Further, TNBC is likely to recur or come back after its been treatment, especially in the few years after treatments.

These numbers are an average of a group of women with TNBC who were studied. However, factors such as the grade and stage of the breast cancer will influence your prognosis. Based on the stage of your TNBC, your age and overall health, your doctor will give you a more precise outlook on your disease. How well you respond to treatment will also affect your prognosis.

Treatment

There is currently no set treatment strategy for TNBC cases, but TNBC is typically treated with a combination of surgery, radiation therapy and chemotherapy. Your doctor determines the best treatment option or combination treatment plan. If you follow the treatment plan that is best for your specific situation, while doing your best to make healthy lifestyle choices such as eating a healthy diet, exercising regularly, and limiting alcohol, you’re doing everything you can to treat the cancer.

  • Chemotherapy is the most common treatment for TNBC, and it can be given either before the surgery to shrink the tumor, or after the surgery to keep the cancer cells from spreading. Most TNBC cases are effectively treated with chemotherapy.
  • Surgery may be done to remove only the tumor, part of the breast, or all of the breast.
  • Radiation therapy kills cancer cells using high-energy rays.

TNBC responds well to chemotherapy because it kills the cells that are dividing quickly throughout the body. When chemotherapy is done before surgery, it is called neoadjuvant therapy. In a small study of women with locally advanced TNBC, two thirds of the women treated with chemotherapy medications before surgery showed no living cancer cells in the tumor when the tumor was removed. In another study, treatment of TNBC with chemotherapy before surgery resulted in the disappearance of all evidence of the disease.

If the tumor has spread or become metastatic, it is usually treated with chemotherapy. Research is needed to determine the best combination of chemotherapy for these cases.

Other treatment options for TNBC include (i) mastectomy, which is the removal of the entire breast and (ii) lumpectomy, which is the removal of a tumor and a bit of normal tissue.

New and Emerging Treatment

Clinical trials are research studies where new medicines are tested in humans to determine how well they work, and if they are safe and effective. In addition to medicines, clinical trials can also test the impact of diet, nutrition or exercise on the return of breast cancer, or if changing your lifestyle could lower your risk for developing breast cancer.

Clinical trials are divided into 4 types:

  • Phase I trials: The goal of this type of study is to find out what is the safe dose of a drug. It also tests the best way a medicine should be given – such as by mouth or by vein. Phase I trials are usually small, and they are open to women with cancer that has spread from the breast.
  • Phase II trials: These studies look further into the safety of the drug. They also test whether the drug is effective. These studies involve up to several hundred people, and are open to women with either early stage or late stage cancer.
  • Phase III trials: The goal of this type of cancer is to compare a new treatment to the standard treatment to see if the new treatment is better. These trials have several hundred to several thousand participants. If a drug passes this phase, it is very likely to be approved by the U.S. Food and Drug Administration (FDA).
  • Phase IV trials: These studies test the long-term side effects of a treatment that the FDA already approved.

There are several medicines that are being developed and tested to treat TNBC.

  • BET Bromodomain Inhibitors are drugs that block cell growth by dislodging the BRD4 and other bromodomain proteins from sections of chromosomes.
  • Immunotherapy Agents such as pembrolizumab and avelumab are drugs that help the immune system to fight cancer by targeting PD-L1, a protein that is more common in TNBC than in other breast cancers. When PD-L1 binds with another protein on the immune system cells, it causes the cell to shut off its ability to attack cancer cells. Thus, drugs are being developed to bind to PD-L1 and allow the immune cells to function normally.
  • Poly (ADP-ribose) polymerase (PARP) Inhibitors such as olaparib are drugs that block PARP, an enzyme that cells use to repair damaged DNA. Cancer cells have damaged DNA, and these cells tend to have very active PARP. To kill the cancer cells, researchers are developing and testing PARP inhibitors, which prevent PARP from working. Since cancer cells can become resistant to chemotherapy, PARP inhibitors may help to lower the chance of resistance and increase the effectiveness of the chemotherapy.
  • DNA Damaging Agents are drugs that disrupt the building blocks of DNA and kill cancer cells. These types of drugs are been developed and tested in the basal-like subtype of TNBC.
  • Anti-angiogenic Agents prevent the growth of blood vessels, which is what cancer cells need in order to survive. Specifically, these agents block vascular endothelial growth factor receptor (VEGFR), which cells use to make new blood vessels that connect the tumor to the surrounding tissues. Examples of VEGF inhibitors include Avastin (bevacizumab) and Sutent (sutinib).

Ask your doctor about clinical trials for TNBC, and if you are suitable to participate in any of them. You can also look at www.clinicaltrials.gov, a website that lists all clinical trials, and at www.cancer.gov/clinicaltrials, which is part of the National Cancer Institute. [There is also a site called breastcancertrials.org but I am not sure if it is recognized as a reliable resource.]

Managing Side Effects

With your cancer treatment, you may experience side effects such as nausea, vomiting, pain, fatigue and hair loss. These effects may be short-term while others last for a longer time. It is very important that you speak with your health care team about which side effects you might experience from your treatment. You will be prescribed medications to manage your side effects, but you have to remember to keep your dosing consistent and timely. In addition to medications to manage your side effects, it is also recommended that you eat healthy, exercise and rest well.

Communicating With Your Medical Team

Being diagnosed with TNBC can be overwhelming. Your health care team, which may include your primary care doctor, a cancer specialist, nurses and social workers, can help you with your concerns. To communicate well with your team:

Write down questions as you think about them. Some examples of questions that you can ask your medical team include:

  • Have you treated other patients with TNBC?
  • What is the cancer stage, grade, and how do they impact my treatment options?
  • What side effects might I have, and how can I prevent or lessen them?
  • Are there long-term effects of the treatment, and how do the risks of the therapy compare to the benefits?
  • Am I eligible for a clinical trial?
  • Should I speak with a professional about genetic testing?
  • Take notes during your appointments. Ask someone to accompany you to your appointments and have them write down the names and locations of professionals that you are referred to. Also, make notes on all medications that you are prescribed.

Genetic Testing

Your chances of developing breast cancer again may be high if you have a family history of breast cancer in both breasts, or if you have a BRCA1 or BRCA2 mutation. Genetic testing may guide your decisions about preventative treatment. Speak to a genetic counselor to find out if genetic testing is right for you. The health care professional can help you understand how your test results can impact several important areas including your follow-up tests, treatment, relationships and insurance coverage.

Managing Your Medical Records and Health Information

Each of the medical professionals who are caring for you will keep a record of your care. However, it is a very good idea for you to keep your own records with information about your medications, surgeries, treatments, treatment schedules, imaging reports, pathology reports, and other details of your care. This way, you will have your complete health history all together. At your hospital appointments, it may be a good idea to record the sessions using a recorder or a phone. You can store your records and the recorded information on computer flash drives or hard drives, in a 3-ring binder or a file folder. You can also consider keeping your health information in a secure online area such as Google Docs, Dropbox so that those whom you trust can access them easily. Choose a system that you think will be easiest for you and your caregivers to keep all of your information in one place and up to date.

Living With TNBC

To help you cope while you’re living with TNBC, you can get emotional support through several ways:

  • Join a support group. Support groups connect you with other people who are coping with similar situations. They are led by professional cancer social workers who specialize in helping people with cancer. You can participate in the support groups in person, on the telephone, or online.
  • Ask for help. Often times, people with cancer do not ask their family and friends for help because they worry that are a burden. Don’t worry, someone will be there for you. Make a list of the things you need help with, for example, grocery shopping, household chores, and/or transportation.
  • Maintain a positive outlook. There is an association between how well patients manage stress and how well they do during their diagnosis and treatment. Connect with your sources of strength, whether it is prayer, meditation, walking or reading. You can also relax your mind and body through breathing and relaxation techniques.

RESOURCES

Below is a list of additional resources that provide information about diagnosis/treatment, complementary and alternative medicine, clinical trials, financial assistance, transportation and other resources.  

Diagnosis/Treatment

 Clinical Trials

 Financial Assistance