This article is supported by funding from Gilead Sciences, Inc.
Nearly 290,000 new cases of breast cancer were 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 noninvasive (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-positive (HR+) 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 (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+/HER2+ breast cancer. Other breast cancers are only positive for either HR or HER2 and are called HR+/HER2- or HR-/HER2+ 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 disease refers to localized and regional breast cancers; these represent earlier stages of cancer that have 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 means the cancer 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 HR+/HER2- metastatic breast cancer.
What Is HR+/HER2- Breast Cancer?
The term HR+ is generally used to describe tumors that are positive for either or both hormone receptors, estrogen (ER+) and progesterone (PR+). These receptors are located on the surface of HR+ cancer cells and may allow them to grow when they interact with their respective hormones.3
Approximately 7 of every 10 breast cancers are HR+/HER2-, making this the most common form of breast cancer.6 Although every cancer is unique, HR+/HER2- breast cancer generally grows slowly.7 As is the case for any cancer, catching the disease early can be associated with potentially improved outcomes for the patient.6 For women who are diagnosed with HR+/HER2- breast cancer that has not spread outside of the breast, nearly all are expected to live at least 5 years after 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 can be physically demanding, affecting a patient’s ability to do housework, cook, shop, walk, exercise, or climb stairs. Maintaining a healthy weight, eating a healthy diet, and engaging in low- or moderate-intensity exercise may help improve a patient’s overall physical health and quality of life.8,9
Patients may also face psychological burdens. It is not uncommon for patients to experience depression, nervousness or anxiety, reduced desire to socialize, and reduced or loss of intimacy with their partner. Methods of coping with psychological distress can include relaxation, meditation, support groups, journaling, or exploring spiritual/religious beliefs, especially if those have helped in the past.10
Treatment Options for HR+/HER2- Breast Cancer
Treatment for HR+/HER2- breast cancer depends on the stage of the tumor, which is based on its size, whether tumor cells are found in nearby lymph nodes and the number of lymph nodes involved, and whether it has spread to other parts of the body.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.11
For patients with HR+/HER2- breast cancer that has metastasized (tumor has spread to other parts of the body), treatment differs depending on whether a patient is experiencing visceral crisis (when cancer stops organs from working as they should) and on menopausal status.12 For visceral crisis, chemotherapy is typically the first treatment.12 For premenopausal women, ovarian ablation or suppression (stopping ovary function by surgical removal or medication) with certain hormone therapy is typically the first treatment.12 For menopausal or post-menopausal women, hormone therapy is typically the first treatment for metastatic HR+/HER2- breast cancer.12
Hormone therapy blocks the body’s ability to produce the hormones estrogen or progesterone or interferes with the effects of these hormones on breast cancer cells, which may slow or stop the growth of these tumors.13 Hormone therapies may be used alone or in combination with other therapies. Choosing the appropriate hormone therapy for each patient depends on a variety of factors, including menopausal status and use of previous hormone therapies.13 Examples of common hormone therapies include Zoladex (goserelin) and Lupron (leuprolide), ovarian suppression drugs; Arimidex (anastrozole), Femara (letrozole), and Aromasin (exemestane), aromatase inhibitors; tamoxifen blocks estrogen from attaching to receptors; and Faslodex (fulvestrant) and Orserdu (elacestrant), block and destroy estrogen receptors.13,14
Some patients with metastatic HR+/HER2- breast cancer may be eligible for treatment with drugs known as targeted therapies.13 These drugs are often used in combination with hormone therapies or in patients whose cancers have certain molecular features that can be targeted by these agents.13 Examples of common targeted therapies include the CDK4/6 inhibitors Ibrance (palbociclib), Verzenio (abemaciclib), and Kisqali (ribociclib); PI3K inhibitor Piqray (alpelisib) for patients with mutations in the PIK3CA gene; PARP inhibitors Lynparza (olaparib) and Talzenna (talazoparib) for patients with BRCA mutations; and the mTOR inhibitor Afinitor (everolimus).13
In addition to patients who are experiencing visceral crisis (severe cancer symptoms in an internal organ), chemotherapy may also be used for patients with metastatic HR+/HER2- breast cancer when hormone and targeted therapies are no longer working.12 These drugs generally work by killing cells that divide and grow quickly, including cancer cells. Examples of chemotherapies include anthracyclines (such as doxorubicin and epirubicin), taxanes (such as paclitaxel), antimetabolites (such as capecitabine or gemcitabine), and microtubule inhibitors (such as eribulin and vinorelbine).13 Similar to hormone therapy, the choice of chemotherapy must be tailored for each patient, often depending on which therapies have been used previously, the patient’s overall health, and the potential side effects.13
Immunotherapies are drugs that are used to increase the activity of the body’s immune system to help it fight cancer.13 Two different immunotherapies may be used in certain patients with metastatic HR+/HER2- breast cancer who have specific biomarkers and have progressed on prior treatment with no other satisfactory alternative treatment options: Keytruda (pembrolizumab) and Jemperli (dostarlimab-gxly).15,16
Antibody-drug conjugates represent another option in treating certain types of metastatic breast cancer. These drugs aim to deliver potent chemotherapies directly to cancer cells that have specific molecules on their surfaces.13,17 Trodelvy (sacituzumab govitecan-hziy, 180 mg for injection) is one such antibody-drug conjugate. 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.17 Trodelvy is a prescription medication used to treat adults with HR+/HER2- 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 2 additional treatments for metastatic disease.17 It is not known if Trodelvy is safe and effective in people with moderate or severe liver problems or in children.
WHAT IS TRODELVY (sacituzumab govitecan-hziy)?
Trodelvy 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 directs the delivery of potent chemotherapy to cells that express low levels of HER2, including tumor cells, and is approved for the treatment of patients with metastatic breast cancers who have low levels of HER2, regardless of hormone receptor status, and who have been previously treated with a chemotherapy for metastatic disease.18
Therapies on the Horizon
It is important to remember that patients should always speak to their oncology team to learn which treatment may be right for them.13 Also, the treatment landscape for HR+/HER2- metastatic 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.19
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.20 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 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.20 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.21 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.21
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 to22; however, trusted coworkers, caring neighbors, religious leaders, and school staff can also play an important role in providing support.23,24 Regardless of the size of the patients’ support network, they may still feel that no one truly understands what they are going through with a diagnosis of metastatic breast cancer.25
Engaging with a community of women who are also living with this disease can reduce patients’ feelings of isolation.26 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, including27:
- 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 families.27 The online sources provided at the end of this article include organizations that can advise about financial assistance programs. Working with a financial navigator may help to reduce the stress and financial hardship associated with a cancer diagnosis.27
All these experts may be able to help patients understand their out-of-pocket costs, what their health insurance plan may cover, and any financial support that may be available from other organizations.28 Financial navigators may be able to help patients set up payment plans, find cost-saving methods for their treatments, and improve access to important healthcare services.28
Receiving a diagnosis of metastatic HR+/HER2- breast cancer may be one of the most challenging events that a patient faces.29 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.
Jenn is a hypothetical patient with metastatic HR+/HER2- breast cancer. Although this story isn’t real, the details are representative of what a patient with a similar diagnosis may face.
Jenn is a 65-year-old woman who lives with her husband in Salt Lake City, Utah. Just over 4 years ago, Jenn was diagnosed with breast cancer that tested positive for estrogen and progesterone receptors and negative for HER2. Initial scans showed that in addition to the tumor in her breast, Jenn’s cancer also spread to her left lung. Together with her physician, Jenn agreed to begin treatment with palbociclib, a CDK4/6 inhibitor, and letrozole, an aromatase inhibitor.12
Her initial treatment had stopped the tumor’s growth. However, 2 years after starting treatment, Jenn’s radiologist found that the tumor had stopped responding to treatment and had started to grow again. Biopsy of the tumor showed that it had acquired a mutation in the gene PIK3CA, and Jenn’s treatment team recommended that she begin treatment with fulvestrant, which blocks and destroys estrogen receptors, and alpelisib, a PI3K inhibitor.12,13
The tumor was responsive to therapy for about a year before starting to grow again. At that point, Jenn’s treatment team recommended that she begin chemotherapy with paclitaxel.12 Approximately 8 months after starting chemotherapy, a PET-CT scan showed that Jenn’s lung tumor had again stopped responding to treatment. Together with her treatment team, Jenn agreed to change chemotherapies to capecitabine, which was effective at stopping the tumor growth for another 6 months until today. Because she had received endocrine-based therapy and at least 2 additional treatments to manage her metastatic HR+/HER2- breast cancer, Jenn and her doctor have agreed that she should begin treatment with Trodelvy (sacituzumab govitecan-hziy).17
Please see full Indications and Important Safety Information above and click to see Important Facts, including Important Warning for low white blood cell count and diarrhea.
- National Cancer Institute. SEER Cancer Stat Facts: female breast cancer. Accessed August 31, 2022. https://seer.cancer.gov/statfacts/html/breast.html
- Lima SM, Kehm RD, Terry MB. Global breast cancer incidence and mortality trends by region, age-groups, and fertility patterns. EClinicalMedicine. 2021;38:100985.
- BreastCancer.org. Understanding your pathology report. Updated August 29, 2022. Accessed August 31, 2022. https://www.breastcancer.org/pathology-report
- 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.
- American Society of Clinical Oncology. Breast cancer: stages. Updated September 2021. Accessed August 31, 2022. https://www.cancer.net/cancer-types/breast-cancer/stages
- National Cancer Institute. SEER Cancer Stat Facts: female breast cancer subtypes. Accessed August 31, 2022. https://seer.cancer.gov/statfacts/html/breast-subtypes.html
- American Cancer Society. Breast cancer hormone receptor status. Updated November 8, 2021. Accessed August 31, 2022. https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-hormone-receptor-status.html
- American Cancer Society. Physical activity and the person with cancer. Updated March 16, 2022. Accessed August 31, 2022. https://www.cancer.org/treatment/survivorship-during-and-after-treatment/be-healthy-after-treatment/physical-activity-and-the-cancer-patient.html
- American Cancer Society. Nutrition for people with cancer. Updated July 15, 2019. Accessed August 31, 2022. https://www.cancer.org/treatment/survivorship-during-and-after-treatment/coping/nutrition.html
- Young Survival Coalition. Metastatic navigator: a young adult’s guide to living with metastatic breast cancer. Updated 2020. Accessed August 31, 2021. https://www.youngsurvival.org/uploads/pdf/guides/metastatic-navigator.pdf
- National Cancer Institute. Breast cancer treatment (adult) (PDQ®)–patient version. Updated April 14, 2022. Accessed August 31, 2022. https://www.cancer.gov/types/breast/patient/breast-treatment-pdq
- Loibl S, Poortmans P, Morrow M, Denkert C, Curigliano G. Breast cancer. Lancet. 2021;397(10286):1750-1769.
- American Society of Clinical Oncology. Breast cancer - metastatic: types of treatment. Updated November 2021. Accessed August 31, 2022. https://www.cancer.net/cancer-types/breast-cancer-metastatic/types-treatment
- Orserdu (elacestrant) tablets. Prescribing Information. Stemline Therapeutics, Inc; January 2023. Accessed February 6, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217639s000lbl.pdf
- Keytruda (pembrolizumab) injection, for intravenous use. Prescribing information. Merck & Co; December 2022. Accessed January 26, 2023. www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf
- Jemperli (dostarlimab-gxly) injection, for intravenous use. Prescribing information. GlaxoSmithKline; April 2022. Accessed February 6, 2023. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/JemperJe/pdf/JEMPERLI-PI-MG.PDF
- Trodelvy (sacituzumab govitecan-hziy) for injection, for intravenous use. Prescribing information. Gilead Sciences; February 2023. Accessed February 5, 2023. www.gilead.com/-/media/files/pdfs/medicines/oncology/trodelvy/trodelvy_pi.pdf
- Enhertu (fam-trastuzumab deruxtecan-nxki) for injection, for intravenous use. Prescribing information. Daiichi Sankyo; November 2022. Accessed January 26, 2023. https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true
- American Society of Clinical Oncology. Breast cancer - metastatic: about clinical trials. Updated November 2021. Accessed February 17, 2023. https://www.cancer.net/cancer-types/breast-cancer-metastatic/about-clinical-trials
- American Cancer Society. Chemotherapy for breast cancer. Updated October 27, 2021. Accessed August 31, 2022. https://www.cancer.org/cancer/breast-cancer/treatment/chemotherapy-for-breast-cancer.html
- American Society of Clinical Oncology. Fertility concerns and preservation for women. Updated September 2019. Accessed February 17, 2023. https://www.cancer.net/navigating-cancer-care/dating-sex-and-reproduction/fertility-concerns-and-preservation-women
- American Society of Clinical Oncology. How cancer affects family life. Updated September 2021. Accessed February 17, 2023. https://www.cancer.net/coping-with-cancer/talking-with-family-and-friends/how-cancer-affects-family-life
- National Cancer Institute. Support for caregivers. Updated January 12, 2023. Accessed January 12, 2023. https://www.cancer.gov/types/breast/patient/breast-treatment-pdq
- National Cancer Institute. Going back to work. Updated January 24, 2019. Accessed February 17, 2023. https://www.cancer.gov/about-cancer/coping/day-to-day/back-to-work
- American Society of Clinical Oncology. Managing emotions. Updated August 2022. Accessed February 17, 2023. https://www.cancer.net/coping-with-cancer/managing-emotions
- American Society of Clinical Oncology. Finding a support buddy. Updated October 2022. Accessed February 17, 2023. https://www.cancer.net/coping-with-cancer/finding-social-support-and-information/finding-support-buddy
- American Society of Clinical Oncology. The oncology team. Updated August 2020. Accessed February 17, 2023. https://www.cancer.net/navigating-cancer-care/cancer-basics/cancer-care-team/oncology-team
- American Society of Clinical Oncology. Cancer and financial toxicity. Updated October 2022. Accessed February 17, 2023. https://www.cancer.net/navigating-cancer-care/financial-considerations/cancer-and-financial-toxicity
- American Society of Clinical Oncology. Counseling. Updated January 2021. Accessed February 17, 2023. https://www.cancer.net/coping-with-cancer/finding-social-support-and-information/counseling