Every December, the largest and most prestigious breast cancer conference in the world takes place in San Antonio, Texas. The San Antonio Breast Cancer Symposium (SABCS) hosts over 10,000 clinicians and scientists from all over the world, and groundbreaking research and clinical advancements are presented each year. In 2022, there were many important updates presented on ongoing clinical trials, but one particular subject seemed to stir up excitement and create a lot of discussion: HER2-low breast cancer.
Until recently, breast cancer was usually divided into 3 basic subtypes: HR+ breast cancer has receptors on the tumor cell surface that use the hormones estrogen and/or progesterone to grow. HER2+ breast cancer has too many copies of a protein receptor called HER2 on the cell’s surface that promotes the rapid growth of cancer cells. Lastly there’s triple negative breast cancer (TNBC), a more aggressive subtype that does not have any of the receptors commonly found in breast cancer. Effective treatments for breast cancer often target receptors on the cancer cell surface by blocking them, either so that they cannot get the “fuel” they need to grow, or to prevent them sending out signals responsible for cell growth and division.
With more sophisticated gene profiling technologies being developed every day, we are starting to recognize that the classification of different breast cancer types is much more diverse than we thought, meaning treatments must become more tailored to individual variations. Previously, breast cancer was considered either HER2-positive or HER2-negative, but now researchers are speaking of a more recent classification known as HER2-low, that has some HER2 receptors on the cell surface, but not enough to be classified as HER2-positive. Up to 60% of tumors that traditionally have been labeled HER2-negative actually have some HER2 and qualify as HER2-low.
HER2-positive cancers are quite fast growing and had a relatively poor prognosis until the game-changing development in the 1990’s of the drug Trastuzumab (also known as Herceptin), a targeted antibody that blocks the HER2 receptors on the tumors and signals the body’s immune system to destroy those cancer cells. Unfortunately, up to a third of patients eventually become resistant to this treatment which can lead to the cancer recurring and spreading. Scientists are constantly seeking new ways to overcome drug resistance, and for these patients, a drug called Trastuzumab Deruxtecan (T-Dxd) has shown promise for metastatic HER2-positive breast cancer. T-Dxd is what is called an antibody conjugate and antibody conjugates are another subject that was significantly explored in San Antonio this year.
Antibody conjugates are a type of drug that is made up of a targeted antibody that binds to a specific type of receptor, attached to a chemotherapy agent. Most types of chemotherapy used by themselves attack all fast growing cells, not just cancer cells. That is why chemo patients’ hair often weakens and falls out. By attaching the chemotherapy to a targeted antibody, the treatment goes directly to the tumor cells like a homing pigeon, with less damage to healthy cells. In T-Dxd, the T stands for Trastuzumab, the HER2 fighting antibody, and the Dxd stands for Deruxtecan which is a type of chemotherapy.
In the various clinical trials that enrolled patients with HER2-low breast cancer, researchers have been focused on finding the best way to treat this intermediary subtype, especially in patients whose cancer has spread to other parts of the body. Interestingly enough, HER2-low tumors have not been shown to respond well to Trastuzumab as classically administered to HER2-positive patients in the first line setting. HER2-low patients can also be hormone-positive or triple negative but this intermediate amount of HER2 receptors simply adds another layer of complexity for establishing the best type of treatment. Much of the trial data presented showed that HER2-low patients treated with T-Dxd had a significant increase in both progression-free survival (PFS) and in overall survival (OS) compared to other therapies.
The inspiring news regarding this antibody conjugate, is that it seems to be beneficial for metastatic patients whose previous treatments stopped working, both in the HER2-positive setting (15-20% of breast cancers), as well as the HER2-low setting (50-60% of breast cancers). It is also being tested in early breast cancer trials. The large and varied population susceptible to being helped by this drug is what has created all the excitement in the breast cancer research community. As always, more research and longer follow-up is needed before any definitive evaluation can be made, but this seems to be a promising direction.
Understanding scientific articles and research can be very overwhelming and confusing for most breast cancer patients. But knowledge is power, and an increased comprehension can lead to better decision making in conjunction with one’s health care team. Please consider applying to the National Breast Cancer Coalition’s Project LEAD, a weeklong course designed to teach the basics of breast cancer science to patient advocates. No prior scientific background is required.