Responsive Innovation in Metastatic Breast Cancer Research

Sanofi scientist Elisabeth de Kermadec in Cambridge, MA

Breakthroughs in breast cancer R&D depend on deep knowledge of the disease, new approaches to drug design and, above all, listening. We asked Sanofi scientist Elisabeth de Kermadec to explain.

"We've seen some important changes in breast cancer treatment in the past decade. Improved diagnostics and new treatments can gain precious time for patients.<sup>1</sup> But for people living with metastatic breast cancer, the constant threat of relapse, of the cancer spreading and progressing, is an unwelcome reality." 

Elisabeth de Kermadec, Clinical Research Director

Before joining Sanofi's oncology R&D team in 2019, I worked as a doctor treating people with breast cancer. I was often struck by how patients with metastatic disease would accept treatments with severe side effects, and how difficult it could be to prepare them for the realities they would face. When cancer spreads to other parts of the body, there is a strong impulse to underestimate the importance of quality of life when considering treatment options. This can have profound effects on the patient and make it harder for their physician to advise on the best course. 

I am passionate about improving treatment options for people with metastatic breast cancer. I've learned firsthand what a huge difference it could make for each patient, and for the people who are by their side through diagnosis and treatment. Drugs that are easier on patients would allow people with metastatic breast cancer to be more present, their care team to focus on emotional and social support, and their doctor to help them find a balance between treatment and quality of life.2

Listening is key

When I joined Sanofi as a clinical director in 2019, I was at first overwhelmed by the scale of its oncology program. I had this sense of a magical machine, with a vast array of expertise and technology, and so many people focused on finding new solutions for patients. New approaches to drug design, like synthetic biology and antibody–drug conjugates, are helping our teams develop medicines to combat drug resistance or minimize damage to healthy tissues. 

But as a clinical director at Sanofi, I could see that listening is the real engine behind responsive innovation. It’s the crucial first step toward meaningful healthcare solutions that address the real needs of patients, including quality of life. 

Technologies that push research further at Sanofi

Biomarkers
Biological clues that can help predict how a patient might respond to a medicine
Protein Degraders
Designing new drugs to target and destroy proteins that help cancers grow
Immunotherapy
Jump-starting the immune system to detect and destroy cancer cells without triggering an autoimmune response
Antibody–Drug Conjugates
Designing antibodies to deliver powerful drugs directly to tumors
Synthetic Biology
Using an expanded genetic alphabet to adjust medicines and reduce their toxic effects

Learn more about Sanofi technology platforms

"Listening" can mean a lot of things at Sanofi, from one-on-one discussions to analyzing real-world data. For me, what stands out is how panels of patients are consulted when the clinical trial is being designed. Listening to understand their daily lives, and their first-hand experiences with research, allows us to focus on what they need most and include people who are representative of the wider patient community.

Treatment Gaps
In a survey by advocacy group Metastatic Breast Cancer (MBC) Alliance<sup>3</sup>, patients expressed frustration at the "trial-and-error" nature of treatment. They want biomarkers that would help their doctor predict the benefits of a treatment for them as an individual. They also want treatments with less toxicity.<sup>4</sup>
Recognition & Support
A diagnosis of metastatic breast cancer is a very different experience from one of earlier stages of breast cancer. A 2017 survey of women with MBC3 underscored the need for more recognition and support for those in later stages of illness.
Economic Disparities
Over 60% of metastatic breast cancer deaths occur in low- to middle-income countries, where women are commonly diagnosed with advanced-stage breast cancer at first presentation.<sup>5,6,7</sup>

Cancer fueled by hormones

We can focus on what matters most to patients by listening closely to their physicians. This has guided our work in estrogen-receptor-positive (ER+) breast cancer, in which estrogen receptors help fuel tumor growth.8 If this form of cancer becomes metastatic, it can become resistant to therapies that have worked for the patient before. Going through several different treatments in rapid succession like this can have a serious impact on quality of life, which is why combatting drug resistance is an important focus for our teams.

We listen to patients and their families, who have consistently voiced their desire to keep visits to the clinic to a minimum–this has been especially true during the pandemic. But treatments for metastatic disease are often administered as an infusion, or into the muscle,9 and that means patients need to visit the clinic regularly. That’s what motivates us to investigate new medications, for example a drug designed to inhibit tumor growth by degrading estrogen receptors.

Hormone receptors and breast cancer

HR+

Breast cancer is not a single disease. The most common types of breast cancer diagnosed today are hormone-receptor positive (HR+), meaning the cancer is fueled by the hormones estrogen or progesterone.10 They can be classified as:

  • Estrogen-receptor positive (ER+) or 
  • Progesterone-receptor positive (PR+).
HR+ and HR–

Breast cancers can also be:

  • Hormone-receptor negative
  • Human epidermal growth factor receptor-2 positive
  • Human epidermal growth factor receptor-2 negative

Breast cancers can also be a combination of these types.

– – –

"Triple negative" breast cancers do not express receptors for estrogen, progesterone, or human epidural growth factor receptor 2.

Every step counts

It has taken the actions of many to get us where we are today, but we must keep up the pace by listening to and hearing every voice. As a clinician caring for people with metastatic disease, it was all too easy to feel that innovation wasn't happening quickly enough. But I know that in the bigger picture, every incremental discovery, every small step toward improving a therapy, can change the lives of patients and their families for the better. I am really lucky to be part of that.

By Elisabeth de Kermadec, Clinical Research Director at Sanofi

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References

  1. Mayer M, Crawford-Gray K (2015) Analysis of quality of life: research on living with MBC. MBC Alliance. Accessed at https://www.mbcalliance.org/wp-content/uploads/Chapter-3-1.pdf on 22 September 2021
  2. Aranda, S., et al. (2005) Mapping the quality of life and unmet needs of urban women with metastatic breast cancer. Eur J Cancer Care 14: 211-22; doi: 10.1111/j.1365-2354.2005.00541.x
  3. MBC Alliance survey results. Accessed at https://www.mbcalliance.org/survey on 22 September 2021
  4. Mayer M, Crawford-Gray K (2015) Analysis of quality of life: research on living with MBC. MBC Alliance. Accessed at https://www.mbcalliance.org/wp-content/uploads/Chapter-3-1.pdf on 22 September 2021
  5. Reeder-Hayes KE, Anderson BO (2017) Breast cancer disparities at home and abroad: a review of the challenges and opportunities for system-level change. Clin Cancer Res 23:2655–2664; doi: 10.1158/1078-0432.CCR-16-2630
  6. Jemal A et al. (2012) Cancer burden in Africa and opportunities for prevention. Cancer 118:4372-4384
  7. International Agency for Research on Cancer and World Health Organization (2020) Latest global cancer data: Cancer burden rises to 19.3 million new case and 10.0 million cancer deaths in 2020 Accessed at https://iarc.fr/wp-content/uploads/2020/12/pr292_E.pdf on 22 September 2022
  8. Clark GM, et al. (1984) Correlations between estrogen receptor, progesterone receptor, and patient characteristics in human breast cancer. J Clin Oncol 2:1102–1109
  9. American Cancer Society. Hormone Therapy for Breast Cancer. Accessed at https://www.cancer.org/cancer/breast-cancer/treatment/hormone-therapy-for-breast-cancer.html on 22 September 2021
  10. Altwegg KA et al. (2021). Role of estrogen receptor coregulators in endocrine resistant breast cancer. Exploration of targeted anti-tumor therapy 2:385–400; doi: 10.37349/etat.2021.00052