Some breast cancers have particular proteins or genetic changes that can be attacked with targeted drugs. These treatments can sometimes attack cancer more precisely than traditional chemotherapy.
The best-known example is HER2-positive breast cancer, which can be treated with drugs specifically targeting HER2. Other targeted treatments are available for some cancers with BRCA or other genetic changes.
Immunotherapy works differently. It helps the body's immune system recognize and attack cancer cells and is useful for some women with triple-negative breast cancer.
These treatments are not appropriate for every breast cancer. Their use depends on testing the cancer—and sometimes inherited genes—to identify the biological characteristics that can be targeted.
HER2-positive breast cancer has unusually high levels of a protein called HER2 that promotes cancer-cell growth. Before effective HER2-targeted drugs became available, these cancers tended to be particularly aggressive.
The introduction of trastuzumab (Herceptin) dramatically changed treatment. Trastuzumab attaches to HER2 and interferes with signals that help the cancer grow. In early HER2-positive breast cancer, adding trastuzumab to treatment can substantially reduce recurrence and improve survival.
Several newer HER2-targeted treatments are now available. These include drugs that block HER2 in different ways and antibody-drug conjugates, which combine a HER2-targeting antibody with a cancer-killing drug that is delivered to the cancer cell.
The choice of HER2-targeted treatment depends on factors including the stage of the cancer, previous treatments, response to treatment, and whether the cancer has spread.
HER2-positive breast cancer is an important example of how understanding the biology of an individual cancer can lead to much more effective treatment.
Some breast cancers occur in women who inherit mutations in BRCA1 or BRCA2, genes that normally help repair damaged DNA. Cancer cells with these mutations already have difficulty repairing DNA.
PARP inhibitors take advantage of this weakness. PARP is another system cells use to repair damaged DNA. By blocking PARP, drugs such as olaparib (Lynparza) can make it much harder for BRCA-mutated cancer cells to survive.
The OlympiA trial studied more than 1,800 women with HER2-negative, high-risk early breast cancer and an inherited BRCA1 or BRCA2 mutation. After standard treatment, women who received olaparib for one year had fewer recurrences and better survival than those who received a placebo.
PARP inhibitors are also used in some women with advanced or metastatic HER2-negative breast cancer and inherited BRCA mutations.
This is another reason why genetic testing can sometimes affect not only a woman's understanding of inherited cancer risk, but also her treatment choices.
Triple-negative breast cancer lacks estrogen receptors, progesterone receptors, and high levels of HER2. Because it does not respond to hormone therapy or traditional HER2-targeted drugs, treatment has historically relied heavily on chemotherapy.
Pembrolizumab (Keytruda) is an immunotherapy drug that helps the immune system recognize and attack cancer cells. It has become an important treatment for some women with triple-negative breast cancer.
For high-risk, early-stage triple-negative breast cancer, pembrolizumab may be given with chemotherapy before surgery and then continued after surgery. In the major KEYNOTE-522 trial, this approach reduced the risk of recurrence or progression and improved overall survival compared with chemotherapy alone.
KEYNOTE-522 – Overall Survival Results
For advanced or metastatic triple-negative breast cancer, pembrolizumab is used in certain patients whose tumors have sufficient levels of a biomarker called PD-L1.
Immunotherapy can produce significant benefits, but it can also cause the immune system to attack normal organs and tissues. The potential benefit therefore needs to be weighed against these sometimes serious side effects.
Breast cancer is not a single disease. Two cancers that look similar under a microscope may respond very differently to treatment because of their biological characteristics.
Testing for estrogen and progesterone receptors and HER2 is standard for invasive breast cancer and helps determine whether hormone therapy or HER2-targeted treatment is appropriate.
Other tests may be important in particular situations. Inherited BRCA1 or BRCA2 mutations can affect whether PARP inhibitors are useful. PD-L1 testing can help determine whether immunotherapy is appropriate for some patients with metastatic triple-negative breast cancer.
As researchers discover additional characteristics of breast cancers, the number of targeted treatments continues to grow.
The practical question is increasingly not simply “What kind of breast cancer do I have?” but “Does my cancer have a characteristic that can be specifically targeted?”
Has my cancer been tested for HER2, hormone receptors, and other relevant biomarkers?
Is there a targeted therapy that is appropriate for my cancer?
Should I have genetic testing for BRCA1, BRCA2, or other inherited mutations?
If you recommend a targeted therapy, how much is it expected to reduce my risk of recurrence or improve survival?
What are the most important side effects and risks?
Is immunotherapy appropriate for my cancer?
Would any additional tumor or genetic testing help identify other treatment options?
Are there circumstances in which less treatment would provide nearly the same benefit?
A useful overview of HER2-targeted drugs and other targeted treatments used for different types of breast cancer.
Explains how trastuzumab targets HER2 and how it is used to treat HER2-positive breast cancer.
The major randomized trial establishing the benefit of olaparib for certain patients with high-risk, HER2-negative early breast cancer and inherited BRCA1 or BRCA2 mutations.
A major randomized trial showing that adding pembrolizumab to chemotherapy improved outcomes in high-risk early triple-negative breast cancer.
Highlights successful treatments that grew out of the Department of Defense Breast Cancer Research Program, including HER2-targeted therapy, and describes promising research areas with new treatments, vaccines, immunotherapies, and diagnostic approaches advancing through clinical trials.