To mark Breast Cancer Awareness Month 2020 this October, FRAME Alternatives Laboratory (FAL) PhD student Wichitra Asanprakit discusses breast cancer statistics in the UK and explains the potential impact of her research project looking at neoadjuvant (before surgery) chemotherapy treatments.
Insight into chemotherapy side effects
Not every chemotherapy regime has the same benefit for every cancer patient, leading to some patients undergoing treatments with unpleasant side effects that have little or no impact on the cancer.
Wichitra’s project demonstrates how the genetics of breast cancer patients could be used to predict the benefits of chemotherapy prior to treatment. This is an example of human relevant research providing the kind of insight that animal research using mice could not.
Nearly 26,000 rodents were used in studies undertaken by the Institute of Cancer Research in 2019, although that is half the number used a decade ago, hopefully signalling a growing realisation of the importance of human focused cancer research.
Breast cancer in the UK
Breast cancer is the most common cancer worldwide. (1) In 2018, there were 2.09 million new breast cancer cases and 627,000 breast cancer related deaths throughout the world. (1, 2) In the UK, there were 55,200 new breast cancer cases every year – approximately 150 cases per day (2015-2017). (3) The incidence of breast cancer in females has increased by 5% over the last decade, putting increased pressure on the NHS to provide healthcare and treatment to these patients. (4) The utilisation of healthcare services for breast cancer costs the UK economy £504 million a year.(5) Additionally, there are many indirect economic costs associated with cancer such as travel costs, time off work and unpaid care by friends and family.
The majority of patients have early stage breast cancer which has a 5-year survival rate of approximately 90% (2013-2017).(6) This is partly as a result of the mammographic breast cancer screening program offered to women aged 50 to 70 in England every 3 years. (7) Breast cancer screening aims to reduce the mortality rate and suffering from breast cancer by detecting early stage cancer in women who do not have any symptoms.
Despite the wide implementation of the screening programme, around 20% of patients still present with large and locally advanced breast cancer (LLABC) which has a 5-year survival rate of 50-60%. (4, 6)
LLABC includes breast tumours larger than 3cm, cancers that involve multiple lymph nodes in the armpit or above and below the collarbone, cancers that involve the skin or the underlying muscle of the chest, and inflammatory breast cancer which is a very aggressive form, presenting with redness and swelling of the skin overlying the breast.
Due to the increased rate of loco-regional (restricted to a localised region of the body) recurrence and risk of systemic metastases (cancer spreading to different parts of the body) after treatment, this group of patients poses a clinical challenge in terms of treatment and subsequent monitoring.
Neoadjuvant chemotherapy (NAC) is increasingly being used as the primary treatment for LLABCs before surgery. It aims to downstage the tumour in advanced disease and reduce tumour size in large breast cancers in order to facilitate surgical treatment and increase the likelihood of breast preservation after the surgery. Only 20-30% of patients, however, achieve a pathological complete response (pCR) which contributes to survival benefit of the patients. The remaining patients receive little clinical benefit and may experience significant morbidity. Predicting the patients who are likely to achieve a pCR before commencing this chemotherapy is, therefore, beneficial in many aspects.
Chemotherapy research project
The FAL is currently collaborating with the Human Biomaterials Resource Centre (HBRC) at the University of Birmingham on a project looking at genetic markers for predicting the success of neoadjuvant chemotherapy (NAC) in breast cancer patients.
The research aims to develop an accurate, reliable and practical predictive factor of a pCR in breast cancer in women undergoing NAC. Whole genome sequencing of breast cancer biopsy specimens from 10 patients with LLABC prior to NAC was performed as a pilot study. The results revealed that the expression of polymeric immunoglobulin receptor (PIGR) gene was significantly increased in breast cancers with pCR following NAC. PIGR expression in breast cancers was further highlighted by research regarding into its predictive ability of a pCR after NAC, using breast cancer core biopsy specimens from a large cohort of breast cancer patients.
Animal models are used in much cancer research. My research, however, utilises human cancer tissue which preserves the structure, mutational load and heterogeneity of the original patient tumour. These properties cannot be observed and fully replaced by animal models thus limiting their translational value to humans. Moreover, cancers induced in animal models don’t imitate how cancers naturally develop in humans and responses to chemotherapy may not resemble those of a human.
The ultimate goal of this research is to translate the findings into clinical practice. By identifying the predictive factor for a pCR, this research will influence a change in LLABC patient care through more personalised targeted treatment of patients who will truly benefit from NAC. This approach can improve patient outcomes, safety and quality of life as well as benefit their families and reduce healthcare costs to the NHS.
1.World Health Organization. Cancer [updated 2018 Sep 12; cited 2020 Aug 20]. Available from: https://www.who.int/news-room/fact-sheets/detail/cancer.
2.Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.
3.Cancer Research UK. Breast cancer statistics [cited 2020 Aug 20]. Available from: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/breast-cancer#heading-Zero.
4.Cancer Research UK. Breast cancer incidence (invasive) statistics [updated 2020 Mar 11; cited 2020 Aug 20]. Available from: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/breast-cancer/incidence-invasive#heading-Three.
5.Laudicella M, Walsh B, Burns E, Smith PC. Cost of care for cancer patients in England: evidence from population-based patient-level data. Br J Cancer. 2016;114(11):1286-92.
6.Cancer Research UK. Breast cancer survival statistics [updated 2020 Apr 2; cited 2020 Aug 20]. Available from: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/breast-cancer/survival#heading-Zero.
7.National Health Service. Overview Breast cancer screening [updated 2018 Mar 27; cited 2020 Aug 22]. Available from: https://www.nhs.uk/conditions/breast-cancer-screening/.