Uncovering the Why of Breast Cancer with LC/MS solutions

Waters Staff

Reading Time: 5 minutes

Chances are that you or someone you know has been directly impacted by breast cancer. With 2,088,849 new cases and 626,679 deaths globally,1 it is the most frequently diagnosed cancer in women in most countries (154 of 185) and is the leading cause of cancer death in women in over 100 countries.

Fortunately, significant strides in breast cancer research and treatments continue to be made, despite those sobering statistics. We continue to learn more and more about the disease. The National Institutes of Health have invested $9B over the last five years in breast cancer research and there were 20K research publications on breast cancer in 2019 alone. We now know that there are mutations in a variety of genes that correlate with the emergence of the disease. Mutations in the BRAC1/2 genes are the best known, but there are mutations in 13 other genes that are associated with breast cancer. And we know that tumors may contain receptors (estrogen, progesterone, or HER2/Neu) that offer more efficacious treatment options for women who have developed cancer. Strides have been made in treating women with breast cancer (anthracyclines, taxanes, 5-fluorouracil, cyclophosphamide, carboplatin) and all major drug companies are pursuing new, more personalized treatments.

All this research has led to great progress and promising trends. Better and more frequent screening, more education, and earlier intervention have combined to increase survival rates. Important societal structures have emerged to support and nurture those with the disease and the loved ones that care for them. The message of early detection and prevention is, thankfully, spreading across the globe.

But, the aching question of “Why?” remains. The causes and mechanisms of why breast cancer emerges, how it grows, and what drives metastases are still largely unanswered questions. Unpacking this domain holds the promise for deeper understanding of disease and mapping routes for prevention, diagnosis, and treatment. But human biology is massively complex. Our 20,000 genes are transformed into 80,000+ proteins and 100,000+ metabolites, many with bioactive isomers and isoforms2,3. And intricate interaction networks connect all of these components through direct or signaling cascades. Our bodies are vibrant entities with millions of joules of biological energy flowing through them. Where to start the inquiry?

At Waters, our focus is to enhance human health and well-being.  In this case, that means deploying our human, scientific, and technology assets to uncover the answers of these increasingly complex questions.  Liquid chromatographic and mass spectrometric (LC/MS) workflows provide distinct benefits for answering the questions to complement the efforts of other technologies, such as genomics, that are investigating orthogonal dimensions of the disease. Our innovations simultaneously measure 100s and 1000s of bioactive molecules and we are using those tools in collaboration with some of the world’s best oncology researchers to hunt down actionable answers to breast cancer.

One significant risk factor for developing breast cancer is weight. In addition to cardiometabolic disease, we know that obesity is associated both with a higher risk of developing breast cancer, particularly in postmenopausal women, and with worse disease outcome for women of all ages4,5. Fat is a sophisticated energy regulation organ, storing and releasing excess energy in the form of triglycerides and communicating with distant organs such as the liver, pancreas, and brain to stimulate or arrest production of biomolecules, such as insulin, that play a role in energy trafficking. Under conditions of chronic energy excess, more and more triglycerides are stored, engorging the fat cells.  It appears that these hypertrophic fat cells can choke off the blood supply to the breast tissue and that, in turn, can lead to hypoxia and death of breast fat cells. Cell death sets off a storm of biochemical signaling and results in a significant inflammatory response.

A compelling story but, in the fractal design of nature, it introduces more questions. What are the signaling cascades? Do the levels change over time? Are there different signals that could let us know that certain tissue is more at risk before? Are those signaling patterns generalizable to other forms of cancer?

These kinds of questions are in the sweet spot for Waters technologies. We can interrogate fat tissue and blood of obese women to discover and quantify biomolecular signatures associated with the mechanisms of breast cancer. We can measure not only the triglyceride levels, for example, but also which triglycerides are present in tissue and blood (there are over 50 different kinds). And measure the hundreds of fatty acids, signaling molecules, and proteins that change and flux with different states of health and disease. And, we are. Working with world leaders in cancer research, we are using our technologies and analytical expertise to understand the changes in the biological energy landscape underwriting cancer and discover diagnostic and prognostic insights to guide more effective intervention.

In continued collaboration with a global network of cancer experts, Waters is harnessing the power of LC/MS to uncover the deeper mechanisms of breast cancer and help answer the question of “Why”. We will continue to do our part to help find the answers to eliminate this disease once and for all.

  1. World Health Organization. Global Health Observatory. Geneva: World Health Organization; 2018. who.int/gho/database/en/. Accessed June 21, 2018
  2. The size of the human Proteome: The Width and Depth. Ponomarkenko, EA et al (2016). Int J Anal Chem. May 19. 7436849
  3. HMDB 4.0: the human metabolome database for 2018. Wishart DS et al (2018). Nucleic Acids Res. 2018 Jan 4; 46 (Database issue): D608-D617.
  4. Association of Body Fat and Risk of Breast Cancer in Postmenopausal Women With Normal Body Mass Index. Iyengar, NM et al. JAMA Oncol. 2019 Feb; 5(2): 155–163
  5. Obesity and Adverse Breast Cancer Risk and Outcome: Mechanistic Insights and Strategies for Intervention. Picon-Ruiz, M et al. CA Cancer J Clin 2017;67:378-397