The best results immunotherapy has achieved so far in breast cancer treatment

Treatments that activate the immune system to attack cancer cells, rather than killing them directly, are called immunotherapy . The idea of treating cancer through the immune system has a history going back 130 years, but it became a reality only in 2011 when ipilimumab was approved for malignant melanoma skin cancer. Since then, these “immune checkpoint inhibitors,” a very specific type of immunotherapy, have shown efficacy and received FDA approval in lung cancer, kidney cancer, bladder cancer, Hodgkin lymphoma, head and neck cancers, bladder cancer and Merkel cell skin cancer. Most recently, immunotherapy has been approved for colorectal cancer and cancers of all organs found to be MSI-high, a type of genetic abnormality. However, “Does immunotherapy work in breast cancer?” was a question that had not received a meaningful answer until ASCO 2017, where results of the I-SPY 2 study were presented.

Breast cancer is divided into 4 main subtypes according to the biological characteristics of the cells. These breast cancer subtypes, which have different treatments, are determined by whether hormone and HER2 receptors are positive.

This phase 2 clinical trial evaluating immunotherapy efficacy in breast cancer enrolled HER2-negative early-stage breast cancer patients, totaling 249. Of these, 69 received the immunotherapy drug pembrolizumab (Keytruda) with standard chemotherapy, while 180 received standard chemotherapy regimens. Among them, 118 had the breast cancer type called triple-negative, which can be difficult to treat.

In breast cancer, chemotherapy is given before surgery to shrink the tumor (neoadjuvant), after surgery to reduce recurrence risk (adjuvant), or in advanced (metastatic) disease to improve survival or quality of life.

The study aimed to measure whether adding the immunotherapy drug pembrolizumab to preoperative tumor-shrinking chemotherapy increased treatment success. Success was assessed through rates of pathological complete response , meaning complete elimination of cancer cells by tumor-shrinking chemotherapy. Achieving a complete response with neoadjuvant therapy is the most important indicator that cancer will not recur in the long term.

Study results

As shown in the figure above, in this HER2-negative breast cancer group, adding pembrolizumab immunotherapy to standard tumor-shrinking chemotherapy regimens increased complete response rates approximately 3-fold. Following these positive results, a trial involving 300 patients in phase-3 was quickly initiated.

Immunotherapies are known as drugs with much less potential for side effects than chemotherapy (see immunotherapy side effects). Although these study results are impressive, pembrolizumab immunotherapy side effects were higher than expected in early-stage breast cancer patients. For example, nausea occurred in %34 receiving chemotherapy plus pembrolizumab and %18 receiving chemotherapy alone; diarrhea in %49 versus %37; and neuropathy, nerve damage in the hands and feet, in %13 versus %4. Among immune-related endocrine side effects, hypothyroidism occurred in %8.7 receiving pembrolizumab and %0.6 in the other group.

In conclusion The I-SPY 2 study is the first to show that immunotherapy may be effective in early-stage breast cancer. It also showed us that immunotherapy combined with chemotherapy may cause more serious side effects and patients need careful monitoring in this respect. We will follow the phase-3 clinical trial results for immunotherapies in early-stage breast cancer treatment for you.