Advances in Breast Cancer Research
A polyploid giant cancer cell (PGCC) from triple-negative breast cancer.
Credit: National Cancer Institute
NCI-funded researchers are working to advance our understanding of how to prevent, detect, and treat breast cancer. They are also looking at how to address disparities and improve quality of life for survivors of the disease.
This page highlights some of what's new in the latest research for breast cancer, including new clinical advances that may soon translate into improved care, NCI-supported programs that are fueling progress, and research findings from recent studies.
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Early Detection of Breast Cancer
Breast cancer is one of a few cancers for which an effective screening test, mammography, is available. MRI (magnetic resonance imaging) and ultrasound are also used to detect breast cancer, but not as routine screening tools for people with average risk.
Ongoing studies are looking at ways to enhance current breast cancer screening options. Technological advances in imaging are creating new opportunities for improvements in both screening and early detection.
One technology advance is 3-D mammography, also called breast tomosynthesis. This procedure takes images from different angles around the breast and builds them into a 3-D-like image. Although this technology is increasingly available in the clinic, it isn’t known whether it is better than standard 2-D mammography, for detecting cancer at a less advanced stage.
NCI is funding a large-scale randomized breast screening trial, the Tomosynthesis Mammographic Imaging Screening Trial (TMIST), to compare the number of advanced cancers detected in women screened for 5 years with 3-D mammography with the number detected in women screened with 2-D mammography.
Two concerns in breast cancer screening, as in all cancer screening, are:
· the potential for diagnosing tumors that would not have become life-threatening (overdiagnosis)
· the possibility of receiving false-positive test results, and the anxiety that comes with follow-up tests or procedures
As cancer treatment is becoming more individualized, researchers are looking at ways to personalize breast cancer screening. They are studying screening methods that are appropriate for each woman’s level of risk and limit the possibility of overdiagnosis.
For example, the Women Informed to Screen Depending on Measures of Risk (WISDOM) study aims to determine if risk-based screening—that is, screening at intervals that are based on each woman’s risk as determined by her genetic makeup, family history, and other risk factors—is as safe, effective, and accepted as standard annual screening mammography.
WISDOM is also making a focused effort to enroll Black women in the trial. Past studies tended to contain a majority of White women and therefore, there is less data on how screening can benefit Black women. Researchers are taking a number of steps to include as many Black women as possible in the study while also increasing the diversity of all women enrolled.
Breast Cancer Treatment
The mainstays of breast cancer treatment are surgery, radiation, chemotherapy, hormone therapy, and targeted therapy. But scientists continue to study novel treatments and drugs, along with new combinations of existing treatments.
It is now known that breast cancer can be divided into subtypes based on whether they contain estrogen and/or progesterone receptors (that is, are hormone receptor, or HR, positive) and whether they have high levels of HER2 protein (HER2 positive).
Hear about challenges in breast cancer research in this excerpt from a Facebook Live event with Dr. Stan Lipkowitz and Dr Alexandra Zimmer of NCI’s Center for Cancer Research.
As we learn more about the subtypes of breast cancer and their behavior, we can use this information to guide treatment decisions. For example:
· The NCI-sponsored TAILORx clinical trial. The study, which included patients with ER-positive, lymph node-negative breast cancer, found that a test that looks at the expression of certain genes can predict which women can safely avoid chemotherapy.
· The RxPONDER trial found that the same gene expression test can also be used to determine treatment options in women with more advanced breast cancer. The study found that some postmenopausal women with HR positive, HER-2 negative breast cancer that has spread to several lymph nodes and has a low risk of recurrence do not benefit from chemotherapy when added to their hormone therapy.
Genomic analyses, such as those carried out through The Cancer Genome Atlas (TCGA), have provided more insights into the molecular diversity of breast cancer and eventually could help identify even more breast cancer subtypes. That knowledge, in turn, may lead to the development of therapies that target the genetic alterations that drive those cancer subtypes.
HR-Positive Breast Cancer Treatment
Hormone therapies have been a mainstay of treatment for HR-positive cancer. However, there is a new focus on adding targeted therapies to hormone therapy for advanced or metastatic HR-positive cancers. These treatments could prolong the time until chemotherapy is needed and ideally, extend survival. Approved drugs include:
· Palbociclib (Ibrance), ribociclib (Kisqali), and everolimus (Afinitor) have all been approved by the FDA for use with hormone therapy for treatment of advanced or metastatic breast cancer. Ribociclib has been shown to increase the survival of patients with metastatic breast cancer.
· Abemaciclib (Verzenio) can be used with or after hormone therapy to treat advanced or metastatic HR-positive, HER2-negative breast cancer. In October 2021, the Food and Drug Administration (FDA) approved abemaciclib in combination with hormone therapy to treat some people who have had surgery for early-stage HR-positive, HER2-negative breast cancer.
HER2-Positive Breast Cancer Treatment
The FDA has approved a number of targeted therapies to treat HER2-positive breast cancer, including:
· Trastuzumab (Herceptin) has been approved to be used to prevent a relapse in patients with early-stage HER2-positive breast cancer.
· Trastuzumab and pertuzumab together can be used in combination with chemotherapy to prevent relapse in people with early-stage HER2-positive breast cancer. Both are also used together in metastatic disease, where they delay progression and improve overall survival.
· Trastuzumab deruxtecan (Enhertu) is approved for patients with advanced or metastatic HER2-positive breast cancer who have previously received a HER2-targeted treatment. A 2021 clinical trial showed that the drug lengthened the time that people with metastatic HER2-positive breast cancer lived without their cancer progressing. The trial also showed that it was better at shrinking tumors than another targeted drug, trastuzumab emtansine (Kadcyla).
· Tucatinib (Tukysa) is approved to be used in combination with trastuzumab and capecitabine (Xeloda) for HER2-positive breast cancer that cannot be removed with surgery or is metastatic. Tucatinib is able to cross the blood–brain barrier, which makes it especially useful for HER2-positive metastatic breast cancer, which tends to spread to the brain.
· Lapatinib (Tykerb) has been approved for treatment of some patients with HER2-positive advanced or metastatic breast cancer, together with capecitabine or letrozole.
· Neratinib Maleate (Nerlynx) can be used in patients with early-stage HER2-positive breast cancer and can also be used together with capecitabine (Xeloda) in some patients with advanced or metastatic disease.
· Ado-trastuzumab emtansine (Kadcyla) is approved to treat patients with metastatic HER2-positive breast cancer who have previously received trastuzumab and a taxane. It's also used in some patients with early-stage HER2-positive breast cancer who have completed neoadjuvant therapy and have residual disease at the time of surgery.
HER2-Low Breast Cancer
A newly defined subtype, HER2-low, accounts for more than half of all metastatic breast cancers. HER2-low tumors are defined as those whose cells contain lower levels of the HER2 protein on their surface. Such tumors have traditionally been classified as HER2-negative because they did not respond to drugs that target HER2.
However, in a recent clinical trial, trastuzumab deruxtecan (Enhertu) improved the survival of patients with HER2-low breast cancer compared with chemotherapy, and the drug has recently received an accelerated approval for use in such patients.
Triple-Negative Breast Cancer Treatment
Triple-negative breast cancers (TNBC) are the hardest to treat because they lack both hormone receptors and HER2 overexpression, so they do not respond to therapies directed at these targets. Therefore, chemotherapy is the mainstay for treatment of TNBC. However, new treatments are starting to become available. These include:
· Sacituzumab govitecan-hziy (Trodelvy) is approved to treat patients with TNBC that has spread to other parts of the body. Patients must have received at least two prior therapies before receiving the drug.
· Pembrolizumab (Keytruda) is an immunotherapy drug that is approved to be used in combination with chemotherapy for patients with locally advanced or metastatic TNBC that has the PD-L1 protein. It may also be used for patients with early-stage TNBC, regardless of their PD-L1 status.
· PARP inhibitors, which include olaparib (Lynparza) and talazoparib (Talzenna), are approved to treat metastatic HER2-negative or triple-negative breast cancers in patients who have inherited a harmful BRCA gene mutation. Olaparib is also approved for use in certain patients with early-stage HER2-negative or triple-negative breast cancer.
· Drugs that block the androgen receptors or prevent androgen production are being tested in a subset of TNBC that express the androgen receptor.
NCI-Supported Breast Cancer Research Programs
Many NCI-funded researchers working at the NIH campus, as well as across the United States and world, are seeking ways to address breast cancer more effectively. Some research is basic, exploring questions as diverse as the biological underpinnings of cancer and the social factors that affect cancer risk. And some are more clinical, seeking to translate this basic information into improving patient outcomes. The programs listed below are a small sampling of NCI’s research efforts in breast cancer.
Breast Cancer Early Detection and Treatment Research
The Breast Specialized Programs of Research Excellence (Breast SPOREs) are designed to quickly move basic scientific findings into clinical settings. The Breast SPOREs support the development of new therapies and technologies, and studies to better understand tumor resistance, diagnosis, prognosis, screening, prevention, and treatment of breast cancer.
The NCI Cancer Intervention and Surveillance Modeling Network (CISNET) focuses on using modeling to improve our understanding of how prevention, early detection, screening, and treatment affect breast cancer outcomes.
The Confluence Project, from NCI's Division of Cancer Epidemiology and Genetics (DCEG), is developing a research resource that includes data from thousands of breast cancer patients and controls of different races and ethnicities. This resource will be used to identify genes that are associated with breast cancer risk, prognosis, subtypes, response to treatment, and second breast cancers. (DCEG conducts other breast cancer research as well.)
The goal of the Breast Cancer Surveillance Consortium (BCSC)Exit Disclaimer, an NCI-funded program launched in 1994, is to enhance the understanding of breast cancer screening practices in the United States and their impact on the breast cancer's stage at diagnosis, survival rates, and mortality.
There are ongoing programs at NCI that support prevention and early detection research in different cancers, including breast cancer. Examples include:
· The Cancer Biomarkers Research Group, which promotes research in cancer biomarkers and manages the Early Detection Research Network (EDRN). EDRN is a network of NCI-funded institutions that are collaborating to discover and validate early detection biomarkers. Within the EDRN, the Breast and Gynecologic Cancers Collaborative Group conducts research on breast and ovarian cancers.
· NCI's Division of Cancer Prevention houses the Breast and Gynecologic Cancer Research Group which conducts and fosters the development of research on the prevention and early detection of breast and gynecologic cancers.
Breast Cancer Health Disparities Research
Black women are more likely to be diagnosed with aggressive subtypes of breast cancer, and they are more likely to die of their disease than White women. To gain an understanding of these disparities, NCI is funding a multi-institution project, the Breast Cancer Genetic Study in African-Ancestry Populations. The genes of Black women with and without breast cancer will be compared to each other, as well as to those of White women who have breast cancer.
The NCI-funded Detroit Research on Cancer Survivors (Detroit ROCS) study will look at the major factors affecting cancer progression, recurrence, mortality, and quality of life among African-American survivors of four different cancers, including breast. Detroit ROCS will examine medical, emotional, social, environmental, and other factors that may affect cancer survival.
Researchers have developed a new tool to estimate the risk of breast cancer in US Black women. The team that developed the tool hopes it will help guide more personalized decisions on when Black women—especially younger women—should begin breast cancer screening. The Black Women’s Health Study (BWHS) Breast Cancer Risk Calculator allows health professionals to estimate a woman’s risk of developing invasive breast cancer over the next 5 years.
Breast Cancer Survivorship Research
NCI’s Office of Cancer Survivorship, part of the Division of Cancer Control and Population Sciences (DCCPS), supports research projects throughout the country that study many issues related to breast cancer survivorship. Examples of studies funded include the impact of cancer and its treatment on physical functioning, emotional well-being, cognitive impairment, sleep disturbances, and cardiovascular health. Other studies focus on financial impacts, the effects on caregivers, models of care for survivors, and issues such as racial disparities and communication.
Breast Cancer Clinical Trials
Breast Cancer Research Results
The following are some of our latest news articles on breast cancer research and study updates:
View the full list of Breast Cancer Research Results and Study Updates
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