By Karuna Jaggar, Former Executive Director and SABCS Guest Writer
Cancer is a complex disease that includes breakdowns in multiple biological systems that allow tumors to grow. Understanding these mechanisms, sometimes referred to as the “Hallmarks of Cancer,” gives researchers insights into both the prevention and treatment of cancer. The Hallmarks of Cancer, as described by Hanahan and Weinberg, include ten common characteristics of all cancers:
- The cells in cancer have become gnomically unstable, with a high frequency of mutations;
- They are frequently found in an inflammatory environment (i.e., surrounding tissue);
- They grow uncontrollably;
- They are able to avoid anti-growth signaling;
- The normal cellular self-destruct mechanism is not functioning properly;
- The cells have bypassed a replication limit that is not functioning properly;
- The metabolic machinery with the cells is not functioning normally;
- The cancerous cells are able to evade detection by the immune system;
- Cells that are oxygen-deprived within a tumor will signal for new blood flow; and
- Malignant cancerous cells invade nearby tissues, and ultimately enter the blood stream or lymph system, which allows them to spread and colonize in other parts of the body.
The ability of cancer to evade the immune system has been studied for many years, in recognition of the 8th hallmark of cancer listed above. The long-standing hope has been that if only doctors could find a way to harness the immune system to recognize and target cancer cells, immunotherapy might be a universal answer to cancer. Despite clear advances in immunotherapy for other cancers, in breast cancer it has felt like immunotherapy has lagged and clinical benefit has not always materialized.
Notwithstanding the general hope and optimism surrounding immunotherapy, these treatments have not been shown to work for many breast cancers, and the treatments come with serious side effects. It’s worth remembering, that while the immune system can protect our health, when it goes unchecked it can also turn against the body. Indeed, many of the deaths from COVID-19 seem to result from an overactive immune response.
There were several major immunotherapy studies done this year, less than two years since the U.S. Food and Drug Administration (FDA) approved the first immunotherapy regimen for breast cancer. On March 8, 2019 the agency granted accelerated approval for the atezolizumab (brand name Tecentriq) for use in combination with chemotherapy for metastatic triple negative breast cancer based on progression-free survival. In September 2020, the FDA issued an alert notifying that atezolizumab (Tecentriq) failed to meet its primary end point in effectively treating the disease, and noted concerns that the chemotherapy nab-paclitaxel should not be replaced with paclitaxel in clinical practice.
This context is important in understanding the immunotherapy updates from this year’s SABCS. Because each study is quite dense, we are sharing data and the key takeaways from the largest immunotherapy studies in separate blog posts:
- Pembrolizumab (Keytruda) updates from the KEYNOTE 355 study
- Atezolizumab (Tencentriq) updates from the IMpassion031 study
- Sacituzumab govitecan (Trodelvy) from the ASCENT trial
Issues that we considered in looking at the results from these studies include:
- Does the immunotherapy help people live longer, improving overall survival?
- What are the side effects from the immunotherapy, including patient reported outcomes?
- How much does treatment cost, and will the people who need the treatment be able to afford it?
So far, despite wonderful responses to treatment by some people, the data on immunotherapy is mixed. We will never let hope—or hype—override the need for demonstrated clinical benefit for people living with breast cancer. We’ll tell you what immunotherapy might mean for you. And we’ll continue to call for more effective, less toxic treatments.