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But… What About Secondary Breast Cancer?

Breast Cancer Awareness Month Campaign was launched over 30 years ago aiming to promote breast awareness, share information about the disease and claim better screening services and treatments.

Despite increasing awareness on breast self-exam and access to annual screening, family history risk assessment and targeted therapies, there are still patients who succumb to the disease. In the UK alone, 31 breast cancer deaths occur every day [1].

Today, much has yet to be accomplished. It is vitally important to raise awareness about the advanced state of the disease which ends up taking lives away. Women and men (do not forget, we all have breast tissue!) who might not be aware at diagnosis that their cancer could come back years after treatment of their primary tumour.

You might have heard about secondary, advanced, Stage IV or metastatic breast cancer. All of these terms refer to the outgrowth of breast cancer cells that spread to other parts of the body (such as bone, liver, lungs and/or brain). Few breast cancer cells are able to survive in these foreign kingdoms far away from the breast. However, those which do survive, do it by entering into a dormant or inactive state, remaining alive for years or even decades.

In Estrogen Receptor-positive (ER+) tumours, this long-term phenomenon known as metastatic dormancy can last up to 25 years [2]. Eventually dormant breast cancer cells make themselves at home and activate their growing abilities, colonising the organ and showing clinically apparent symptoms (Figure 1).

 

 

Figure 1. Breast cancer progression. Breast tumours are diagnosed in 54,722 women and 387 men every year in the UK [1].  Breast self-exam helps to spot any signs of what breast cancer can look like (12 symptoms of breast cancer by KnowYourLemons Foundation). Despite surgery and treatment, some cancer cells that escape earlier from the breast and spread to distant organs remain alive in an inactive state for many years (dormant disease, undetectable lesions). Somehow, some dormant cancer cells start growing in secondary organs (active disease) causing the development of specific symptoms in patients. These red flags can be recognised (learn more about secondary breast cancer symptoms using After Breast Cancer Diagnosis Infographics). These bigger lesions (macrometastases) become detectable in the clinic and are unfortunately incurable. After a survival period of 2-5 years, 31 patients die of secondary breast cancer every day in the UK [1].

 

However, this dormant behaviour is not that rare in nature and it is not restricted to breast pathological conditions. For example, hibernation, a state of minimal activity, is essential for some animals to survive extreme winters; there is also a dormant state called diapause during embryonic development that occurs in over 130 species of mammals; and it is also found in plants and insects. Moreover, metastatic dormancy is observed in other cancer types. Regardless of the context, this resting strategy is crucial to survival.

As researchers, we are still learning about the spreading of cancer cells and what triggers their growth in secondary organs (altogether known as metastasis). But something we all agree is that during this multi-step process, cancer cells are influenced by their surroundings. Therefore, understanding the interactions between cancer cells and their environment will offer novel therapeutic windows of intervention to modulate and control cancer cell behaviour.

 

Understanding secondary breast cancer in the lab

 

As an undergrad I became really interested in how cancer cells that break away from the primary site survive therapies and are able to re-grow a tumour in distant locations. That is why I decided to visit Prof Rob Clarke’s lab during my PhD studies to learn about the tumour-initiating ability of breast cancer cells (also known as Cancer Stem Cells). Studying in Manchester made even more sense given its historical role in cancer research, and in particular in breast cancer (e.g.: the “Manchester Method”, first clinical trial of Stilboestrol, first clinical use of Tamoxifen and the development of Fulvestrant at AstraZeneca in Macclesfield).

Later on, I had the opportunity to bring together my scientific curiosities and develop my current postdoctoral research to address an unmet need in secondary breast cancer.

My investigation focuses on understanding how dormant breast cancer cells survive in other organs and how their surroundings (cells from the secondary site) regulate their awakening. In particular, how a protein called NOTCH regulates dormancy or activity of ER+ breast cancer cells that spread to bone.

To address this question, I put all my efforts in developing better models to comprehend the advanced state of the disease using our Patient-Derived Xenografts (PDXs) and implementing novel technologies to monitor cancer cell spreading and growth state in distant sites. Targeting dormant breast cancer cells with tumour-initiating abilities, the seeds of metastasis, will prevent recurrences, control outgrowing active disease and eventually patients dying of secondary breast cancer.

Today, in normal circumstances, Breast Biology would be hosting our usual “a bit noisy” Bake Sale for “Wear It Pink Day” in the OCRB foyer. This national fundraising campaign helps to raise awareness and enable us to continue working on vital breast cancer research which will have a long-term impact in patients’ lives.

Last, but not least, to all patients suffering secondary breast cancer: You are not alone, we are working hard to understand this advanced state of the disease to offer you novel therapeutic options that tackle the major hurdle of this disease. We think of you every day!

 

References

[1] Cancer Research UK. Breast cancer statistics. CRUK http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-bycancer- type/breast-cancer (2017).

[2] Pan et al, EBCTCG, N Eng J Med. 2017, 377(19):1836-1846


Category: MCRC

Dr Angélica Santiago Gómez is a Postdoctoral Researcher in Prof Rob Clarke’s lab at the Oglesby Cancer Research Building, University of Manchester. Her research is funded by Alfonso Martin Escudero Foundation, Rosetrees Trust, Breast Cancer Now and The Christie NHS Foundation Trust.

Read more posts by Angélica Santiago Gómez