Breast cancer remains one of the two most-common types of cancer in the world, according to the World Health Organization. It’s the fourth-leading cause of cancer-related deaths annually. And more than 281,000 people will be diagnosed with it in the United States alone, during any given year. Breast cancer is one of a few cancers for which an effective screening test, mammography, is available. MRI (magnetic resonance imaging), ultrasound, and clinical breast exams are also used to detect breast cancer, but not as routine screening tools. 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.
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 that respond differently to various types of treatment.
Hormone receptor (HR) positive: HR-positive breast cancers are those that contain the estrogen receptor (ER) and/or progesterone receptor (PR). These cancers grow in response to these hormones and can be treated with hormone therapies.
Human epidermal growth factor receptor 2 (HER2) positive: HER2-positive breast cancers are those that have high amounts of the HER2 protein; they can be HR positive or HR negative. These cancers can be treated with therapies that target HER2.
Triple-Negative Breast Cancer: 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.
Some treatments now being used are:
In April 2020, the FDA approved the drug sacituzumab govitecan-hziy (Trodelvy) to treat triple negative breast cancer that has spread to other parts of the body. Patients must have received at least two prior therapies before receiving the drug.
PARP inhibitors work by blocking a protein that is used to repair damage to DNA that occurs during cell division. These drugs, which include olaparib (Lynparza) and talazoparib (Talzenna), effectively target TNBC caused by certain inherited BRCA gene mutations or other alterations that lead to defects in DNA damage repair. They are also approved for metastatic ER-positive, HER2-negative breast cancers in patients who have inherited a harmful BRCA gene mutation.
Immunotherapy drugs have shown some promise in a small number of breast cancers, particularly those that are triple negative. Some data suggest that patients may be more likely to respond to immunotherapy if their tumor expresses the protein PD-L1 or if it has a large number of mutations.
Scientists are also studying whether combining a variety of drugs with immunotherapy will work better than immunotherapy alone. The immunotherapy drug atezolizumab (Tecentriq) is approved to be used with chemotherapy in patients with metastatic TNBC that expresses the PD-L1 protein.
Drugs that block the androgen receptors (AR) or prevent androgen production are being tested in a subset of TNBC cancers that express the AR.
HR-Positive Breast Cancer Treatment: Targeted therapy uses drugs or other substances to attack cancer cells with less harm to normal cells. There is a new focus on adding targeted therapies to hormone therapy for advanced or metastatic HR-positive breast cancer. 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 recently for use with hormonal therapy for treatment of advanced or metastatic breast cancer.
- Abemaciclib (Verzenio) can be given with hormonal therapy or alone after treatment with hormonal therapy to women with advanced or metastatic ER-positive, HER2-negative breast cancer. These combinations are also being tested to see if they can prevent a relapse after treatment of early-stage ER-positive disease.
- Alpelisib (Piqray) is approved to be used in combination with hormonal therapy to treat HR-positive and HER2-negative breast cancers that have a mutation in the PIK3CA gene.
The FDA has approved a number of targeted therapies to treat HER2-positive breast cancer, including:
- Trastuzumab (Herceptin) and pertuzumab (Perjeta) can be used in combination with chemotherapy for both early and advanced breast cancer. Trastuzumab has also been approved to prevent a relapse in patients with early-stage HER2-positive breast cancer.
- Ado-trastuzumab emtansine (Kadcyla) is an FDA-approved treatment for advanced HER2-positive breast cancer.
- Lapatinib (Tykerb) has been approved for treatment of HER2-positive metastatic breast cancer. However, a study that tested adding lapatinib to chemotherapy and trastuzumab to treat early-stage breast cancer did not show a significant improvement in outcomes.
- 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.
Targeted therapies have transformed our approach to HER2+ breast cancers, and offer an opportunity to cure stage IV breast cancer in certain patients. Ultimately, the goal is to help more women survive breast cancer (if not avoid it altogether). But as more women survive, more attention needs to be paid to the long-term impact of treatment. So what lies ahead in the crystal ball? Researchers’ hopes include better targeted therapies, better tests to detect breast cancer, better ways to identify aggressive tumors and deliver treatment to the right patients, more funding for research and more women willing to participate in clinical trials. Neuropathy, lymphedema, pain and sexual dysfunction can impact survivors for years after treatment ends. About a third of women experience moderate to severe fatigue up to 10 years later.