Dr. Sandra Dunn co-authored this blog with Dr. Mary Rose Pambid, Clinical Research Manager at Phoenix Molecular Designs.
Every October since 1985, communities have united for one common cause: to raise awareness about breast cancer. This month, as communities, organizations, and commercial goods “go pink,” we will spend another 31 days celebrating the successes of those who have beat the disease, and remember those we have lost. However, while we celebrate and mourn the people who have dealt with breast cancer, we must also celebrate the tremendous strides made by scientific and medical professionals in treating breast cancer, as well as look to the future and examine how we can further combat the disease.
From the 1800s and 1900s…
Just 20 years ago, breast cancer was subdivided into three different subtypes: hormone receptor-positive, HER2 positive, and triple negative breast cancer (TNBC). But what did breast cancer research and treatment look like before this categorization?
The 19th century saw some of the most important discoveries in history, particularly for surgeons and oncologists. As ethics came to the forefront of science, bringing along anesthesia and other surgical staples, more and more theories about breast cancer proved to be more accurate than the accusations of the past—for one, that breast cancer could be triggered by hormonal factors; additionally, that mastectomies were semi-reliable options for removing the tumor and reducing the chance of a second bout of disease.
It was the 20th century that saw the most radical advancements in breast cancer research and treatment led by women. In the 1940s, for example, mammograms became a staple of preventative women’s health, followed soon after by Dr. Jane C. Wright’s chemotherapy research demonstrating efficacy against breast cancer. In 1962, Dr. Dora Richardson of Imperial Chemical Industries, now known as AstraZeneca, synthesized tamoxifen, a drug that would go on to be the first targeted therapy against hormone-receptor positive breast cancer. Tamoxifen inhibited the estrogen receptor, a protein that drives approximately 70% of breast cancers. While the landmark creation of tamoxifen occurred in 1962, it would be another 15 years before it was approved by the U.S. FDA (Food & Drug Administration) for breast cancer treatment. Tamoxifen did more than treat breast cancer for thousands of women; it also opened the floodgates for targeted therapies. Richardson’s research is still referenced today as biotechnology professionals explore more alternatives for breast cancer treatment. Unfortunately, tamoxifen was not the magic bullet cure for all breast cancer subtypes leading to an outcry for new breast cancer approaches.
Breast cancer patients with HER2+ expressing cancers have also seen the revolutionary advancement of precision therapies. Michael Shepard, Dennis J. Slamon, and Axel Ullrich collaborated on breast cancer cell research, working tirelessly to develop and refine an innovative breast cancer therapeutic. In 1992, the first patient was treated and six years later the end result was Herceptin, an antibody that blocks a cancer-causing protein, and the first therapy of its kind. Along with reducing the risk of recurrence in treated individuals, Herceptin is also credited with lengthening survival time for patients in both metastatic and early stages of the disease.
The keystone of their research, and the information that led to Herceptin’s development was the scientific revelation that certain genes create a disposition to cancer. Therefore, scientists and physicians around the world turned their attention to treating the cause rather than the symptoms.
In September of 2019, the Lasker Foundation awarded Shepard, Slamon, and Ullrich with the 2019 Lasker-DeBakey Clinical Medical Research Award for their efforts to produce Herceptin. The award further solidifies how much Herceptin has remarkably changed breast cancer survival, particularly for women with HER2+ cancers. Developed therapies took a breast cancer diagnosis from a death sentence to a beatable disease for many patients.
All of these research developments, particularly those that dealt with receptors, ushered in the dawn of CDK4/6 inhibitors, the first of which was approved in 2015 under the label Ibrance. Two others soon followed, Kisqali and Verzenio. What is common to each of these medicines is that they were approved in combination with the hormone blocker Fulvestrant. Across all of these discoveries and advancements, one important lesson stood out—that combination therapies are most effective for the treatment of complex diseases such as metastatic breast cancer. True to form, the combination of Tecentriq plus Paclitaxel was approved as the first immunotherapy for the first-line treatment of untreated metastatic TNBC.
…to Tomorrow and the Next Day
Looking at a past riddled with misconceptions and uncharted territory, it is easy to see that we have come a long way. Between 1975 and 2015, we saw a 40% drop in breast cancer mortality rates. Today, there are more than 3.8 million breast cancer survivors. Data like this shows that through research, advocacy, and education, we can combat this disease. However, that does not mean the journey is over yet. Even today, in 2019, over 260,000 women in the U.S. alone are expected to be diagnosed with invasive breast cancer, and over 42,000 women are expected to pass away from breast cancer complications. Strikingly, 113 people die of metastatic breast cancer each day in the U.S. alone. What’s more, race still plays a factor in the effectiveness of breast cancer therapeutics, with white women experiencing more improvements than their non-white counterparts— for instance, black women are 7 times more likely to die of this disease than Caucasian women which we will address in a future post. This is an important challenge before us, and one that needs much more research and attention if we are going to truly move the needle on future breast cancer outcomes. So, while we have certainly come a long way, there is still plenty more ground to cover.
Phoenix Molecular Designs (PMD) has focused particularly on TNBC, a variant with a high therapeutics resistance rate. Having just received approval to go to clinical trials with PMD-026, an innovative TNBC therapy, PMD moves forward into a hopeful future. Back when Herceptin was first produced, I was a graduate student who greatly admired Dr. Dennis Slamon and his team. He is a hero of mine given his perseverance in the face of skepticism. There was doubt surrounding whether Herceptin would work or not. However, like all great pioneers, his tenacity and vision lit the dark days of uncertainty. Not much has changed in that regard, but I have also grown and learned and come into my own, particularly when it comes to breast cancer research and treatment. Today, I am carving my own path, one that is paved by prior success in our field, yet one I can also call my own.