A Brief Guide to Triple-Negative Breast Cancer

A Brief Guide to Triple-Negative Breast Cancer

October 2022 Vol 8 No 5

This article is supported by funding from Gilead Sciences, Inc.

Nearly 290,000 new cases of breast cancer are estimated to be diagnosed in women in the United States in 2022.¹ This makes breast cancer the most common cancer among American women. Although breast cancer remains the leading cause of cancer-related death in women worldwide, earlier diagnosis and improved treatments have steadily reduced the death rate in the United States over the past 30 years.^1,2

Many people know something about breast cancer, but not everyone understands that each breast cancer, and each patient, is unique. When people think of breast cancer, they often think of invasive breast cancer. Unlike non-invasive (also known as in situ) disease, the term “invasive cancer” means that the cancer cells have grown from inside the milk duct or the milk gland into nearby breast tissue.³

Invasive breast cancer is characterized by its molecular and clinical features, which refer to the different genes and proteins that are expressed in the tumor. These genetic and molecular features affect how the cancer of an individual patient grows and responds to treatment. For example, hormone receptor (HR)-positive cancers have proteins that function as receptors for 2 hormones—estrogen and/or progesterone.³ The attachment of either or both of these hormones to their receptors helps the cancer to grow. Other types of breast cancers may have increased amounts of a receptor called human epidermal growth factor receptor 2, or HER2, which helps these forms of breast cancer to grow.³

Different types of breast cancers can have different combinations of these receptors. Some breast cancers have estrogen and/or progesterone receptors and HER2, and are called HR-positive and HER2-positive breast cancer. Other breast cancers are only HR-positive or only HER2-positive and are called HR-positive or HER2-positive breast cancer, respectively.

Another type of breast cancer does not have any of these 3 receptors, meaning it has no receptors for the estrogen hormone, progesterone hormone, or HER2; it is therefore called triple-negative breast cancer (or TNBC).⁴

Breast cancers are also characterized by the stage of the disease, which affects their prognosis (future outlook) and treatment. Stage I, II, or III refers to localized and regional breast cancers; these represent earlier stages of cancer that has not spread beyond the breast, the lymph nodes in the armpit, or the collarbone area.^3,5 Stage IV refers to advanced cancer and is called metastatic breast cancer, which has spread from the breast to other parts of the body, such as the lungs, liver, bones, or brain.^3,5

Understanding the differences between the various types of breast cancers is important, but it can also be challenging. This article aims to help patients and their caregivers understand metastatic triple-negative breast cancer.

What Is Triple-Negative Breast Cancer?

Triple-negative breast cancer is not the most common form of invasive breast cancer, but it is not rare. Between 10% and 20% of breast cancers are the triple-negative type.⁴ Unlike other forms of breast cancer, which are more often found in older individuals, triple-negative breast cancer is more common in young women under age 40.⁶

Triple-negative breast cancer is also more common in African-American women than in other ethnic groups and in women with BRCA1 or BRCA2 mutations (which are genetic alterations that increase the risk for breast cancer) than in those without these mutations.^6,7

Although every cancer is unique, triple-negative breast cancer is generally an aggressive cancer that progresses fast and has a high risk of recurrence (coming back) or spreading (metastasizing) to other parts of the body beyond the breast.⁸

As is the case for any cancer, catching the disease early can be associated with potentially improved outcomes for the patient. For women who are diagnosed with triple-negative breast cancer that has not spread outside the breast, most (more than 9 in 10) are expected to live at least 5 years after their diagnosis.⁶ However, the survival rate decreases for women who are diagnosed with metastatic disease.⁶

Living with Metastatic Breast Cancer

Living with metastatic breast cancer is physically and emotionally demanding. The cancer symptoms and treatment side effects can affect patients’ physical functioning, such as their ability to do housework, cook, shop, walk, exercise, or climb stairs. Maintaining a healthy weight, eating right, and engaging in low-intensity or moderate-intensity exercise may help to improve the patient’s overall health and quality of life.^9,10

Patients may also face psychological challenges because of their diagnosis and treatment. Many patients have depression, anxiety, a reduced desire to socialize, and a reduced or loss of desire for intimacy with their partner after a cancer diagnosis.

Methods of coping with such psychological distress include relaxation, meditation, finding support groups, journaling, and exploring spiritual or religious beliefs, especially if those techniques have helped in the past.¹¹

Treatment Options for Triple-Negative Breast Cancer

Treatment for triple-negative breast cancer depends on the staging of the tumor, which describes its size, whether the cancer cells are in nearby lymph nodes and the number of lymph nodes involved, as well as whether the cancer has spread to other organs.⁵

For small and invasive tumors that have not spread (or metastasized), surgery followed by radiation is the common treatment. For larger tumors that have not metastasized, chemotherapy may also be used before surgery (called neoadjuvant therapy) to shrink the tumor or after surgery (called adjuvant therapy) to prevent recurrence.¹²

For patients whose tumors have spread to other parts of the body, chemotherapy may be the first therapy given.¹² Because triple-negative tumors do not have high levels of the receptors involved in other types of breast cancer, hormone therapy that targets the estrogen receptor or progesterone receptor or treatments that target HER2 may not be helpful for those with triple-negative breast cancer. Nevertheless, triple-negative breast cancer can respond to traditional chemotherapy, which works by killing cells that divide and grow quickly, including cancer cells.¹³

Chemotherapy

Current guidelines recommend the use of chemotherapy drugs as the first treatment option for patients with metastatic triple-negative breast cancer.^13-16 In general, these chemotherapies are used sequentially to avoid the side effects that are seen when those drugs are used in combination.^15,17

Chemotherapy drugs called anthracyclines (such as doxorubicin and epirubicin) or taxanes (such as paclitaxel and docetaxel) are usually used as the first treatment options.¹⁴

Other chemotherapies that may be used for initial treatment include capecitabine, gemcitabine, eribulin, and vinorelbine.¹⁴ For patients with triple-negative breast cancer that is associated with the BRCA1 or BRCA2 mutation, carboplatin or cisplatin may be used.¹⁴ In cases when combination therapy is needed, cyclophosphamide or fluorouracil may be added as the second drug.¹⁴

Targeted Therapies

In recent years, different types of treatments have been approved by the FDA for use in some patients with triple-negative breast cancer. Targeted therapies, which target unique molecules specific to certain cancers, are more recent options for treating cancer.

Lynparza (olaparib) and Talzenna (talazoparib) are targeted therapies that are effective against cancers with BRCA1 or BRCA2 mutation.^18,19 These 2 drugs are approved by the FDA for use in patients with metastatic triple-negative breast cancer that carries one of these mutations, although olaparib should only be used as a second-line treatment after initial treatment with chemotherapy.^14,18,19

Immunotherapy

Another more recent drug is Keytruda (pembrolizumab), an immunotherapy used to increase the activity of the body’s immune system that is approved for the treatment of patients with metastatic triple-negative breast cancer.²⁰ This immunotherapy can be used as a neoadjuvant (before surgery) treatment, in combination with chemotherapy, for patients with high-risk, early-stage triple-negative breast cancer, and then may be continued alone after surgery (adjuvant treatment).^14,20

Keytruda may also be used in combination with chemotherapy for patients with cancer that is locally recurrent but that cannot be removed by surgery (unresectable) or in patients with metastatic disease, as long as their tumors express the target molecule PD-L1.^14,20

Antibody–Drug Conjugates

Finally, Trodelvy (sacituzumab govitecan-hziy, 180 mg for injection) is part of a class of drugs called antibody–drug conjugates.²¹ Trodelvy directs the delivery of potent chemotherapy to cells that have the Trop-2 molecule on their surface, which is common in certain cancer cells.²¹ Trodelvy is a prescription medicine used for the treatment of triple-negative breast cancer that is metastatic or that cannot be removed by surgery in adults who have received 2 or more previous treatments, including at least 1 treatment for metastatic disease.²² It is not known if Trodelvy is safe and effective in patients with moderate or severe liver problems or in children.²² (Article continues following the Important Safety Information, including Important Warning, below.)

WHAT IS TRODELVY?

Trodelvy^® (sacituzumab govitecan-hziy) is a prescription medicine used to treat adults with:

triple-negative breast cancer (negative for estrogen and progesterone hormone receptors and HER2) that has spread to other parts of the body (metastatic) or cannot be removed by surgery, and who have received two or more prior treatments, including at least one treatment for metastatic disease.
hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer that has spread to other parts of the body or cannot be removed by surgery, and who previously received endocrine therapy and at least two additional treatments for metastatic disease.

It is not known if Trodelvy is safe and effective in people with moderate or severe liver problems or in children.

IMPORTANT SAFETY INFORMATION

Trodelvy can cause serious side effects, including low white blood cell count and diarrhea:

Low white blood cell count (neutropenia) which is common and can sometimes be severe and lead to infections that can be life-threatening or cause death. Your healthcare provider should check your blood cell counts during treatment. If your white blood cell count is too low, your healthcare provider may need to lower your dose, give you a medicine to help prevent low blood cell count with future doses of Trodelvy, or in some cases may stop Trodelvy. Your healthcare provider may need to give you antibiotic medicines if you develop fever while your white blood cell count is low. Call your healthcare provider right away if you develop any of the following signs of infection: fever, chills, cough, shortness of breath, or burning or pain when you urinate.
Severe diarrhea. Diarrhea is common and can be severe. Severe diarrhea can lead to loss of too much body fluid (dehydration) and kidney problems. Your healthcare provider should monitor you for diarrhea and give you medicine as needed to help control it. If you lose too much body fluid, your healthcare provider may need to give you fluids and electrolytes to replace body salts. If you develop diarrhea during your treatment with Trodelvy, your healthcare provider should check to see if it may be caused by an infection. Your healthcare provider may decrease your dose or stop Trodelvy if your diarrhea is severe and cannot be controlled with anti-diarrheal medicines.

Call your healthcare provider right away the first time that you get diarrhea during treatment with Trodelvy; if you have black or bloody stools; if you have symptoms of dehydration, such as lightheadedness, dizziness, or faintness; if you are unable to take fluids by mouth due to nausea or vomiting; or if you are not able to get your diarrhea under control within 24 hours.

Do not receive Trodelvy if you have had a severe allergic reaction to Trodelvy. Ask your healthcare provider if you are not sure.

Allergic and infusion-related reactions which can be serious and life-threatening. Tell your healthcare provider or nurse right away if you get any of the following symptoms during your infusion of Trodelvy or within 24 hours after: swelling of your face, lips, tongue, or throat; hives; skin rash, itching, or flushing of your skin; fever; difficulty breathing or wheezing; lightheadedness, dizziness, feeling faint, or pass out; or chills or shaking chills (rigors).

Nausea and vomiting are common with Trodelvy and can sometimes be severe. Before each dose of Trodelvy, you will receive medicines to help prevent nausea and vomiting along with medicines to take home with instructions about how to take them. Call your healthcare provider right away if you have nausea or vomiting that is not controlled with the medicines prescribed for you. Your healthcare provider may decide to decrease your dose or stop Trodelvy if your nausea and vomiting is severe and cannot be controlled with anti-nausea medicines.

Before receiving Trodelvy, tell your healthcare provider about all of your medical conditions, including if you:

have been told that you carry a gene for UGT1A1*28, which can increase your risk of getting side effects with Trodelvy, especially low white blood cell counts, with or without a fever, and low red blood cell counts.
have liver problems.
are pregnant or plan to become pregnant. Trodelvy can harm your unborn baby. Your healthcare provider should check to see if you are pregnant before you start receiving Trodelvy. Trodelvy may cause fertility problems in females, which could affect your ability to have a baby. Talk to your healthcare provider if fertility is a concern for you.

Females who can become pregnant should use effective birth control during treatment and for 6 months after your last dose of Trodelvy. Talk to your healthcare provider about birth control choices that may be right for you during this time. Tell your healthcare provider right away if you become pregnant during treatment with Trodelvy.
Males with a female partner who can become pregnant should use effective birth control during treatment and for 3 months after your last dose of Trodelvy.

are breastfeeding or plan to breastfeed. It is not known if Trodelvy passes into your breastmilk and can harm your baby. Do not breastfeed during treatment and for 1 month after your last dose of Trodelvy.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Certain medicines may affect the way Trodelvy works.

The most common side effects of Trodelvy include decreased white blood cell (leukocyte and lymphocyte) and red blood cell counts, feeling tired or weak, hair loss, constipation, increased sugar levels in the blood, decreased protein levels (albumin) in the blood, decreased appetite, changes in kidney function test, increased levels of enzyme called alkaline phosphatase in the blood (test for liver or bone problems), and decreased levels of magnesium, potassium, and sodium in the blood.

These are not all of the possible side effects of Trodelvy. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Please click to see Important Facts about Trodelvy, including Important Warning.

Enhertu (fam-trastuzumab deruxtecan-nxki) is another antibody–drug conjugate that has been studied in some patients with triple-negative breast cancer to direct the delivery of potent chemotherapy to cells that express low levels of HER2, including tumor cells.²³

It is important to remember that patients should always speak to their oncology team to learn which treatment may be right for them. Also, the treatment landscape for triple-negative breast cancer is continuing to expand. Many clinical studies are ongoing, and interested patients should speak to their oncology team to learn more about investigational therapies and whether they are eligible to join a clinical trial.

What Can you Expect from Treatment?

Cancer treatments can cause a variety of side effects, depending on the particular treatment, the dose, and the duration of therapy; these side effects are different for every medication and may vary for each patient.²⁴ Patients should ask for a list of potential side effects that are associated with their medication. If patients suspect that they have a treatment-related side effect, they should not hesitate to tell that to their care team.

Potential side effects that can occur from cancer treatment may include hair loss; nail changes; mouth sores; loss of appetite or weight changes; nausea and vomiting; diarrhea; fatigue; hot flashes and/or vaginal dryness; nerve damage; and increased risk of bruising, bleeding, or infections.²⁴ Patients should know that their care team may provide therapies to prevent or lessen the impact of certain side effects (for example, by prescribing medications that prevent nausea and vomiting); this is why it is important to raise these issues right away with the care team.

Young women who have been diagnosed with breast cancer may question if their diagnosis or treatment can affect their ability to become pregnant and have children. Women who are considering becoming pregnant and having children in the future are advised to raise these issues with their doctor before starting cancer treatment, which may affect their fertility.

How to Find Support

A strong support network can help patients maintain a good quality of life. Friends and family members often come to mind when we think about who to turn to, although trusted co-workers, caring neighbors, religious leaders, and school staff can also play an important role in providing support. Regardless of the size of patients’ support network, they may still feel that no one truly understands what they are going through with a diagnosis of metastatic breast cancer.

Engaging with a community of women who are also living with this disease can reduce patients’ feelings of isolation. Links to several patient support sources are provided at the end of this article. The care team is also a crucial source of support throughout a patient’s treatment journey.

Aside from oncology doctors and nurses, who are cancer specialists, patients may have interactions with other professionals, including:

Palliative care specialists, who manage the patient’s symptoms and treatment side effects
Genetic counselors, who help to decide what genetic tests, if any, the patient needs, and help patients to interpret the test results
Social workers, who can help with the emotional aspects of cancer and any financial or family issues that arise
Nurse navigators or patient navigators, who can help coordinate care and appointments

In addition, many patients may have concerns and difficulties with the financial impact of a breast cancer diagnosis on them or on their family. The online sources provided at the end of this article include organizations that can advise about financial assistance programs. Working with a financial navigator can also help to reduce the stress and financial hardship associated with a cancer diagnosis.

All these experts can help patients understand what their out-of-pocket costs are and what their health insurance plan may cover, as well as any financial support that may be available from other organizations. Financial navigators can help patients set up payment plans, find cost-saving methods for their treatments, and improve access to important healthcare services.

Keeping Positive

Receiving a diagnosis of metastatic triple-negative breast cancer may be one of the most challenging events that a patient faces. Although women are often pressured to maintain a positive outlook during such time, they should feel free to be themselves, allowing themselves to experience the entire range of human emotions—from hopefulness and joy to sorrow and despair. Nevertheless, being optimistic can often help people feel better overall, and may even help patients cope with some of the challenges they face with a cancer diagnosis.

Mary’s Journey

Mary is a hypothetical patient with metastatic triple-negative breast cancer. Although this story is not real, the details are representative of what a patient with a similar diagnosis may face.

Mary is a 42-year-old mother of 2 who lives in Atlanta, Georgia. Nearly 2 years ago, Mary was diagnosed with breast cancer that was negative for the estrogen and progesterone receptors and for HER2, or triple-negative breast cancer. After her tumor was removed by surgery, Mary and her doctor agreed that she should receive adjuvant chemotherapy (additional chemotherapy after surgery). So, Mary had 4 treatment cycles of doxorubicin plus cyclophosphamide, followed by 12 weeks of paclitaxel.¹⁴

Six months ago, Mary started complaining of shortness of breath and noticed that she was losing weight, although she was not dieting. Her radiologist performed a PET-CT scan and saw that Mary had several new masses in her lungs. A biopsy of one of the masses confirmed that Mary’s triple-negative breast cancer metastasized (spread) to her lungs.

Mary’s treatment team recommended that she receive another chemotherapy regimen of albumin-bound paclitaxel plus carboplatin.¹⁴ Before the first cycle of chemotherapy, Mary’s doctors gave her anti-nausea medications, to be taken 30 to 60 minutes before her chemotherapy treatment. Working together with her treatment team, Mary found that the side effects of her treatment became slightly more manageable.

Mary had a new scan, which showed that her metastatic triple-negative breast cancer had stopped responding to treatment. Because she had received 2 previous systemic treatments, including one for metastatic disease, Mary and her doctor agreed that she should begin treatment with Trodelvy (sacituzumab govitecan-hziy).

Please click to see Important Facts, including Important Warning for low white blood cell count and diarrhea, and Important Safety Information above.

Patient Resources

American Cancer Society
www.cancer.org

CancerCare
www.cancercare.org

Metastatic Breast Cancer Alliance
www.mbcalliance.org

Metastatic Breast Cancer Network
http://mbcn.org

National Cancer Institute
www.cancer.gov

National Comprehensive Cancer Network
www.nccn.org/patientresources

References

National Cancer Institute SEER Program. Cancer stat facts: female breast cancer. https://seer.cancer.gov/statfacts/html/breast.html. Accessed July 11, 2022.
Lima SM, Kehm RD, Terry MB. Global breast cancer incidence and mortality trends by region, age-groups, and fertility patterns. EClinicalMedicine. 2021;38:100985. doi: 10.1016/j.eclinm.2021.100985. Accessed July 11, 2022.
Breastcancer.org. Understanding your pathology report. Updated June 29, 2022. www.breastcancer.org/pathology-report. Accessed July 11, 2022.
Saraiva DP, Guadalupe Cabral M, Jacinto A, Braga S. How many diseases is triple negative breast cancer: the protagonism of the immune microenvironment. ESMO Open. 2017;2(4):e000208. doi: 10.1136/esmoopen-2017-000208. Accessed June 21, 2022.
American Society of Clinical Oncology. Breast cancer: stages. Cancer.Net. September 2021. www.cancer.net/cancer-types/breast-cancer/stages. Accessed July 11, 2022.
American Cancer Society. Triple-negative breast cancer. Updated March 1, 2022. www.cancer.org/cancer/breast-cancer/about/types-of-breast-cancer/triple-negative.html. Accessed July 11, 2022.
Shimelis H, LaDuca H, Hu C, et al. Triple-negative breast cancer risk genes identified by multigene hereditary cancer panel testing. J Natl Cancer Inst. 2018;110(8):855-862.
Cancer Treatment Centers of America. Triple-negative breast cancer. Updated June 24, 2022. www.cancercenter.com/cancer-types/breast-cancer/types/rare-breast-cancer-types/triple-negative-breast-cancer. Accessed July 11, 2022.
American Cancer Society. Physical activity and the person with cancer. Updated March 16, 2022. www.cancer.org/treatment/survivorship-during-and-after-treatment/be-healthy-after-treatment/physical-activity-and-the-cancer-patient.html. Accessed July 11, 2022.
American Cancer Society. Nutrition for people with cancer. Updated July 15, 2019. www.cancer.org/treatment/survivorship-during-and-after-treatment/coping/nutrition.html. Accessed July 11, 2022.
Young Survival Coalition. Metastatic navigator: a young adult’s guide to living with metastatic breast cancer. 2020. www.youngsurvival.org/uploads/pdf/guides/metastatic-navigator.pdf. Accessed July 11, 2021.
National Cancer Institute. Breast cancer treatment (adult) (PDQ)–patient version. Updated April 14, 2022. www.cancer.gov/types/breast/patient/breast-treatment-pdq#_707. Accessed July 11, 2022.
O’Reilly D, Al Sendi M, Kelly CM. Overview of recent advances in metastatic triple negative breast cancer. World J Clin Oncol. 2021;12(3):164-182.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Breast Cancer. Version 4.2022. June 21, 2022. www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed July 11, 2022.
Cardoso F, Senkus E, Costa A, et al. 4th ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4). Ann Oncol. 2018;29(8):1634-1657.
Moy B, Rumble RB, Come SE, et al. Chemotherapy and targeted therapy for patients with human epidermal growth factor receptor 2–negative metastatic breast cancer that is either endocrine-pretreated or hormone receptor–negative: ASCO guideline update. J Clin Oncol. 2021;39(35):3938-3958.
Cardoso F, Castiglione M; for the ESMO Guidelines Working Group. Locally recurrent or metastatic breast cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2009;20(suppl 4):iv15-iv18.
Lynparza (olaparib) tablets, for oral use [prescribing information]. AstraZeneca Pharmaceuticals; March 2022. www.azpicentral.com/pi.html?product=lynparza_tb. Accessed June 21, 2022.
Talzenna (talazoparib) capsules, for oral use [prescribing information]. Pfizer; October 2021. https://labeling.pfizer.com/ShowLabeling.aspx?id=11046. Accessed June 21, 2022.
Keytruda (pembrolizumab) injection, for intravenous use [prescribing information]. Merck & Co; August 2022. www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf. Accessed August 24, 2022.
Bardia A, Hurvitz SA, Tolaney SM, et al; for the ASCENT Clinical Trial investigators. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021;384(16):1529-1541.
Trodelvy USPI (sacituzumab govitecan-hziy) for injection, for intravenous use [prescribing information]. Gilead Sciences; February 2023. www.gilead.com/-/media/files/pdfs/medicines/oncology/trodelvy/trodelvy_pi.pdf. Accessed February 21, 2023.
Modi S, Jacot W, Yamashita T, et al; for the DESTINY-Breast04 trial investigators. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9-20.
American Cancer Society. Chemotherapy for breast cancer. Updated October 27, 2021. www.cancer.org/cancer/breast-cancer/treatment/chemotherapy-for-breast-cancer.html. Accessed July 11, 2022.