by Dr Elaine
In November 2016, two reports highlighted the gravity of cancer trends in women worldwide.
The American Cancer Society conducted an analysis  that concluded a 60% increase in cancer deaths (5.5 million per year) in women was expected by 2030 – it now kills 1 in 7 women (3.5 million in 2012), the 2nd highest cause of death after cardiovascular disease. The Lancet paper  estimated a doubling in new breast cancer cases (3.2 million per year) and a 25% rise in new cervical cancer diagnoses (0.7 million per year) by 2030. Overall, there were 6.7 million new cancer cases (incidence) in women in 2012, which is expected to increase to 9.9 million per year by 2030.
The highest toll was in women from low- and middle-income countries, where a significant proportion of cancers are largely preventable, or can be detected and treated early – breast, colorectal, lung and cervical. Compared to high-income countries, a smaller proportion of cancer cases are diagnosed and treated, and a bigger proportion dies. Women in these countries are also increasingly being exposed to known cancer risk factors that correspond with ‘rapid economic transition’, e.g. obesity, physical inactivity, unhealthy diet, postponing motherhood. Therefore, cancers that were once more common in high-income countries are now becoming more prevalent.
The Singapore Cancer Registry’s ‘Trends in Cancer Incidence in Singapore 2010-2014’  reported that in women, breast, uterine, ovarian and cervical cancers were ranked 1st, 4th, 5th and 10th, respectively, in terms of new cases diagnosed. As regards cancer deaths, breast cancer ranked 1st, ovarian 7th, cervical 8th, and uterine did not rank in the top 10. The overall pattern mirrors that of developed countries. These numbers tell us that in Singapore, breast cancer is the commonest and deadliest cancer in women. When considering men and women together, in terms of incidence, breast cancer is narrowly beaten to 2nd place by colorectal cancer, and is 4th in cancer death rankings after lung, colorectal and liver cancer.
According to a Ministry of Health website , where Singapore’s disease burden is concerned, cancer is placed 2nd after cardiovascular disease. The complexity of cancer care, the innovation and use of novel and effective drugs, and society’s expectation of the provision of affordable and yet state-of-the-art healthcare, have all contributed to the enormity of cancer’s socioeconomic impact.
Through the years, breast cancer incidence in Singapore has been steadily increasing . As measured by age-standardised incidence rates (ASIR, per 100,000 per year) from 1975 to 2014, it had tripled from 23.8 to 64.6. Several factors may explain this phenomenon, e.g. early detection with screening programmes (BreastScreen Singapore), and changing patterns of risk factors (outlined earlier), according to the country’s economic transition spanning the last 4 decades. Mortality rates, as measured by age-standardised mortality rates (ASMR, per 100,000 per year), on the other hand, have plateaued and remained steady from the 1990s to the present, 13.4 to 13.7 – this is interpreted as a reflection of the successful implementation of effective treatment. Despite this, breast cancer is still the top cause of cancer death in women.
Ovarian cancer incidence has similarly been increasing, doubling from ASIR 7.3 to 12.8 in the last 40 years, whereas mortality rates have been stable since the 1990s, with ASMR remaining at 4.
Uterine cancer incidence has also described an uptrend, having more than tripled over 40 years, from ASIR of 4.1 to 14.6. The mortality trend has stayed quite steady, with ASMR ranging between 0.6 and 1.6.
Cervical cancer is the only female cancer that has been decreasing in incidence, with a high of ASIR 16.6 in the 1970s, and subsequently halving to the present with ASIR 7. Mortality rates also decreased from ASMR of 6.4 to 2.3. Along with other developed countries, this has been attributed to the success of our national screening programme through cervical smear tests (CervicalScreen Singapore). The human papilloma virus (HPV) vaccines [5,6] are also expected to have a beneficial effect on cervical cancer prevention on a population basis.
The increasing trend of incidence of breast, uterine and ovarian cancer is worthy of note. Equally notable is their mortality rates, which have been in status quo for 20 years.
Put simply, the problem of cancer may be tackled by preventing the preventable ones, intervening early for those detected early (screening programmes), and for those in the advanced stages, keeping the disease in its tracks without further progression, i.e. improving treatment. The lattermost point was made most obvious with the advent of immunotherapy, where total eradication of cancer (cure) was not needed for patients to lead long lives of good quality. Intriguingly, there is a concept in parallel in traditional Chinese medicine where one tries to achieve a state of living in harmony with one’s disease.
Apart from cervical cancer, which has a robust association with a virus (HPV), the other female cancers do not have clear aetiology. The oft-cited association is with female hormones and their cognate receptors, which is tied in alongside with reproductive factors. For example, hormone replacement therapy (HRT) was shown to increase the risk of developing breast cancer in post-menopausal women , long-term exposure to estrogen is thought to be associated with the development of endometrial cancer , and nulliparity has been suggested as one of the factors associated with ovarian cancer .
Obesity was recently highlighted by the World Health Organisation as a global health problem . Epidemiological studies have supported an association with the development of cancer, especially breast cancer in post-menopausal women . In Singapore, the most recent national health survey  also noted an increasing trend in body mass index (BMI). If mechanistic connections between obesity and female hormone molecular pathways were to be more firmly established, this will extend the areas of research for the purposes of prevention, prognostication and therapeutics in female cancers.
Publicly-funded research efforts in Singapore seem to have largely concentrated on the Asian cancers, i.e. lung cancer in non-smokers (epidermal growth factor receptor [EGFR] mutations), hepatocellular carcinoma (hepatitis virus), and gastric cancer (Helicobacter pylori, refrigeration of food). Perhaps it is time to shine the research spotlight on the commonest and deadliest cancer in women. Given the investments made in Singapore’s research infrastructure, and the high numbers of breast cancer cases, there is a good chance that Singapore would be able to make significant headway in this sphere, even in the face of stiff global competition.
- World Cancer Congress, 31 October – 3 November 2016, Paris, France
- Ginsburg O, et al. The global burden of women’s cancers: a grand challenge in global health. Lancet 2016 Nov 1. pii: S0140-6736(16)31392-7. doi: 10.1016/ S0140-6736(16)31392-7
- https://www.nrdo.gov.sg/docs/librariesprovider3/default-document-library/ cancer-trends-report-2010---2014_web.pdf?sfvrsn=0
- https://www.moh.gov.sg/content/moh_web/home/statistics/Health_ Facts_Singapore/Disease_Burden.html
- FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med 2007, 356: 1915
- Paavonen J, et al. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet 2009, 374: 301
- Rossouw JE, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002, 288: 321
- Persson I, et al. Risk of endometrial cancer after treatment with oestrogens alone or in conjunction with progestogens: results of a prospective study. BMJ 1989, 298: 147
- Stewart LM, et al. In vitro fertilization, endometriosis, nulliparity and ovarian cancer risk. Gynecol Oncol 2013, 128: 260
- WHO World Health Organization Fact Sheet for World Wide Prevalence of Obesity. World Health Organization 2015
- Renehan AG, et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008, 371: 569
- National Health Survey 2010, Singapore. Epidemiology and Disease Control Division, Ministry of Health, Singapore 2011
About the Author
Dr Lim Hsuen Elaine is a Senior Consultant in the Division of Medical Oncology at the National Cancer Centre Singapore. Her interests are centred on breast, gynaecological and lung cancers.