One of the primary goals of breast cancer research is to personalize the treatment of the disease, tailoring therapies to the specific characteristics of each patient’s cancer.
“The future of breast cancer therapy is tied to the idea of individualizing treatment for each patient—not only to the stage and subtype of the cancer but also to a patient’s response to prior therapy, as well as the molecular makeup of the tumor cells and state of the patient’s immune system,” says Sara Tolaney, MD, MPH, associate director of the Susan F. Smith Center for Women’s Cancers at Dana-Farber and director of clinical trials in the Institute’s Breast Oncology Program. “Research being done today is increasingly making that possible.”
Here are some examples of where where investigators have recently made headway.
Triple-negative breast cancer
In a landmark phase III clinical trial, investigators found that combining an immunotherapy agent with chemotherapy outperformed chemotherapy alone in patients with metastatic triple-negative breast cancer that carries the PD-L1 protein. (Triple-negative breast cancer lacks receptors for estrogen, progesterone, and the HER2 protein.) The trial, dubbed IMpassion130, found that patients who received the combination therapy had a longer survival, on average, than those who received chemotherapy alone. It marked the first time that immunotherapy and chemotherapy have been shown to work in synergy for patients who have few other treatment options. The data also demonstrated that the addition of immunotherapy was beneficial to patients whose tumors carry the PD-L1 receptor, and will help doctors better tailor therapy to those who will benefit.
HER2-positive breast cancer
Results of the recently published KATHERINE clinical trial promise to change treatment for women with an early stage of this type of cancer, which tests positive for the HER2 protein. The trial found that patients treated with the drug Trastuzumab-DM1 (also known as T-DM1) after surgery had a significant reduction in risk of recurrence of their cancer compared to patients treated with standard therapy, the drug trastuzumab (also known as Herceptin). The participants had all received chemotherapy with trastuzumab prior to surgery to reduce the size of their tumors but still had residual tumor cells found in their breast at the time of surgery. Trastuzumab is an antibody that binds to, and blocks, HER2. T-DM1 is a “conjugate” drug that fuses trastuzumab to a powerful chemotherapy drug, emtansine. The conjugate works by carrying emtansine directly to HER-bearing tumor cells and destroying them. T-DM1 will likely become a standard option for women with residual disease after preoperative chemotherapy in the next few months.
While the KATHERINE study examined escalating therapy for patients who had residual disease at the time of surgery, there is also interest in studying de-escalating therapy for patients who have no residual tumor detected. A prime example is the DAPHNE clinical trial led by Dana-Farber’s Eric Winer, MD, and Ada Waks, MD. The trial, which is open to patients with stage II or III breast cancer that is HER2-positive, treats patients with paclitaxel, trastuzumab, and pertusumab prior to surgery, and, if they have no residual tumor at surgery, they receive no further chemotherapy but instead receive antibody-based therapy with trastuzumab and pertuzumab.
Estrogen receptor-positive breast cancer
In patients with this type of breast cancer, which grows in response to estrogen, the addition of drugs known as CDK4/6 inhibitors to endocrine therapy can lengthen the period in which the disease is in remission and extend overall patient survival in a subset of patients, clinical data shows. There also is data suggesting that the oral drug alpelisib, which targets the PI3K pathway in cancer cells, can improve the duration of disease control when added to endocrine therapy in patients with hormone receptor-positive breast cancer that also has a PI3K mutation.
Early invasive estrogen receptor-positive breast cancer
In the PALLAS trial led by Dana-Farber physician-investigator Erica Mayer, MD, MPH, investigators are studying whether palbocyclib—a CDK4/6 inhibitor—plus estrogen-blocking therapy is more effective in reducing the chance of breast cancer returning than estrogen-blocking therapy alone. Although the trial has finished accruing patients, another study is investigating a different CDK4/6 inhibitor, abemaciclib, in a similar setting.