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Cancer Epidemiology The International Journal of Cancer Epidemiology, Detection, and Prevention journal homepage: www.cancerepidemiology.net
Review
Breast cancer in South Asia: A Bangladeshi perspective Mohammad Sorowar Hossain a,d,*, Shameema Ferdous b, Henrike E. Karim-Kos c a
BRAC University, Department of Mathematical and Natural Sciences, Dhaka, Bangladesh University of Dhaka, Bangladesh c Department of Public Health, Erasmus MC University Medical Centre, Rotterdam, The Netherlands d Biotechnology Division, Incepta Pharmaceutical Ltd, Dhaka, Bangladesh b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 1 May 2014 Received in revised form 13 July 2014 Accepted 3 August 2014 Available online xxx
South Asian countries are facing a hidden breast cancer epidemic. A significant proportion of the breast cancer cases occur in premenopausal women. Knowledge of the various aspects of breast cancer in different geographical regions is limited in South Asia. In this article, we review the Bangladeshi perspective of the epidemiology, risk factors, pathology, diagnosis and treatment of breast cancer. As in other developing countries, because of the lack of breast cancer awareness in Bangladeshi population and inadequate access to health care, most patients are diagnosed at an advanced stage of the disease. Early detection has a crucial impact on overall treatment outcomes. To battle against breast cancer in resource-limited countries like Bangladesh, it is not feasible to set up a parallel health service system solely dedicated to cancer. Therefore, a cost-effective public health strategy is needed which could reach a large number of women in the country. Considering all these issues, we propose an innovative femalebased primary healthcare approach focused on awareness, screening and early detection of breast cancer in Bangladesh. This preventive strategy could be a model for other resource-limited developing countries. ß 2014 Elsevier Ltd. All rights reserved.
Keywords: Breast Bangladesh Cancer Awareness Primary healthcare South Asia Epidemiology
1. Introduction Breast cancer is the most common cancer in women worldwide. Even though the incidence of breast cancer in developing countries is lower that in their Western counterparts, it is rising rapidly. According to GLOBOCAN estimates, more than half (52.9%) of 1.67 million new breast cancer cases were diagnosed in developing countries in 2012 [1], while the corresponding figure for 1980 was only 35% [2]. Although in developed countries breast cancer is mainly a disease of postmenopausal women (50 years), almost half of all breast cancer cases (45%) in developing countries in 2010 were diagnosed in women of reproductive age (15–49 years) [2]. In Asia, the incidence of breast cancer peaks among premenopausal women in their forties, whereas among postmenopausal women in Western countries it peaks in their sixties [3]. The mortality of breast cancer is significantly higher in developing countries than in high-income countries. In 2012 nearly 62% of deaths associated with breast cancer occurred in developing countries [1].
* Corresponding author at: Department of Mathematics and Natural Sciences, BRAC University, 66 Mohakhali, Dhaka 1212, Bangladesh. Tel.: +880 2 8824051 4x4080; fax: +880 2 8810383. E-mail address: [email protected] (M.S. Hossain).
South Asia, the home of approximately 588 million women over 15 years of age [4], faces a growing breast cancer epidemic, as the incidence of breast cancer is increasing dramatically [5]. Information concerning the epidemiology, biology, and different environmental backgrounds of breast cancer are scarce in South Asia. None of the South Asian countries have central cancer registries which could provide comprehensive nationwide data. All populationbased epidemiological data in this region have been obtained from 25 Indian population-based cancer registries (that cover only 7.5% of the total Indian population) and a single Pakistani cancer registry (coverage 1%) [6,7]. An estimate of over 200,000 new breast cancer cases occurred in South Asia in 2012, and approximately 97,500 breast cancer patients died [1]. Currently breast cancer has overtaken cervical cancer as the most common cancer in South Asian women [1]. Despite current or future efforts, increases in breast cancer incidence in developing countries are expected because of the increasing lifespan resulting from efficient management of infectious diseases, and increasing adaptation to a Westernized life style [8]. With a population of over 163 million, Bangladesh is one of the most densely populated countries in the world [4]. Females have outnumbered males (84.1 versus 79.5 million) in the Bangladeshi population. About 45 million women are at reproductive age, while 13.5 million women are 50 years old [4]. As in other South
http://dx.doi.org/10.1016/j.canep.2014.08.004 1877-7821/ß 2014 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Hossain MS, et al. Breast cancer in South Asia: A Bangladeshi perspective. Cancer Epidemiology (2014), http://dx.doi.org/10.1016/j.canep.2014.08.004
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Asian countries, the life expectancy of Bangladeshi women has increased significantly in recent years from 59 years in 1990 to 70 years in 2011 [9]. Women are the key drivers of the Bangladesh economy and of its social transformation through their enormous contribution in the clothing industries [10] and in microcredit- and microfinance-based development programs [11]. Healthy women are vital for healthy families and communities. However, women’s problems generally get a lower priority in Bangladeshi society. Although Bangladesh has made enormous progress in the healthcare sector – especially related to infectious diseases, as recently highlighted by Lancet [12] – the issue of cancer is given lower priority at both policy and research levels [13]. In this review, we aim to present the current scenario of breast cancer in Bangladesh and suggest a primary healthcare-based innovative strategy for the prevention of breast cancer that could be a model for other low-income countries as well. 2. Epidemiology of breast cancer in Bangladesh Not much information on breast cancer in Bangladesh is available. So far no effort has been made toward creating population-based cancer registries or a central cancer registry to provide comprehensive nationwide data. Therefore, the incidence and prevalence of breast cancer is mostly unknown. However, according to GLOBOCAN estimates based on the extrapolation of Indian data, 14,836 new breast cancer cases were diagnosed in 2012, with an age-standardized incidence rate (ASR) of 21.4 per 100,000 [1]. This figure is likely to be an underestimate since many cases are missed due to lack of awareness, low level of education, misconceptions, poor socioeconomic status, insufficient access to health care, and poor governance. In West Bengal, India (which has a similar culture and population structure), the incidence of breast cancer is similar to that in Bangladesh (ASR 25.2 per 100,000) [14]. The only hospital-based cancer registry tracks new cancer cases systematically in Bangladesh at the National Institute of Cancer Research and Hospital (NICRH). According to an NICRH report, 5255 breast cancer cases were diagnosed during the period 2005– 2010; the mean age of the breast cancer patients was 41.8 years (age range 15–94 years) and over 56% of the cases were women of reproductive age (15–44 years) [15,16]. Similarly, in our neighboring country (India), premenopausal patients constitute about 50% of all breast cancer patients [17]. The higher proportion of premenopausal cases in Bangladesh might be due to the fact that the overall population is much younger than in high-income countries, and possibly missing cases of older women who often feel shy about seeking medical help as well as getting lower priority for treatment compared to younger family members in South Asian countries. The same pattern of a higher proportion of premenopausal cases was also seen among South Asian immigrants in the UK and US [18–20], although the incidence is significantly higher compared to women in their country of origin
(Table 1) [14,21]. A recent study has shown that the age-specific incidence rate of breast cancer is significantly lower in low-income countries (LICs) than in high-income countries (HICs). The incidence of premenopausal cases is about twice as high in HICs (ASR 29.4 versus 12.8 per 100,000) as LICs, whereas the incidence of postmenopausal cases is five-fold higher in HICs (307.6 versus 65.5 per 100,000) [22]. Hence, it has been suggested that the global differences in incidence rate of breast cancer are likely due to the differences in the level of exposures to various reproductive and lifestyle risk factors [22]. Since there is no national registry of cause of death in Bangladesh or of patients’ follow-up systems in hospitals, it is not possible to know about the mortality and survivorship of breast cancer. Nonetheless, GLOBOCAN has estimated that 7142 women died of breast cancer in Bangladesh in 2012 (ASR 11 per 100,000) [1]. Apart from this, a maternal health survey estimated that cancer was responsible for 21% of all women’s deaths in the reproductive age range [23]. Another verbal autopsy study showed that 62% of all deaths associated with breast cancer were in women under 50 years old [24]. 3. Risk factors Some reproductive factors (age at menarche, menopause and first pregnancy, breastfeeding, parity) and non-reproductive factors (menopausal hormone therapy, family history of cancer, body mass index, alcohol intake, and others) have been linked with breast cancer risk [25]. Compelling evidence suggests that certain factors are known to reduce the risk of breast cancer, including increased parity and duration of breastfeeding [26], older age at menarche [27], and lower body mass index [28]. In contrast, use of menopausal hormone therapy [29,30], greater alcohol consumption [31], older age at menopause [27], and a positive family history [32] are known to increase the risk of breast cancer. No case–control studies have been conducted on breast cancer risk factors in the environmental context of Bangladesh. However, well known reproductive factors may not be strongly associated with the breast cancer burden in Bangladesh, where the majority of breast cancer cases are premenopausal. Marriage at an early age, breastfeeding for a longer period of time, and multiple births are the common features in Bangladeshi society. For females, the mean age at first marriage is 18.7 years [33]. Almost all Bangladeshi babies are breastfed for the first year of life, and 90% of these children receive breast milk until the age of 20–23 months [34]. Data from the NICRH cancer registry show that over 93% of all breast cancer patients (n = 5255) were married. Altogether, over 78% of them were multiparous (having given birth two or more times; 56%) and grand multiparous (having given birth five or more times; approximately 22%) [15,16]. In contrast, only about 9% of the cases were nulliparous. Most of the female patients registered at NICRH came from poor family backgrounds since nearly 80% of
Table 1 Characteristics of breast cancer in Bangladesh as compared to other countries. Features
Bangladesh
India
South Asian (SA) immigrant in UK/US
UK/US
Incidence (ASR per 100,000)
21.4
25.8[1]
95 in UK, 92.9 in US [1]
Mean age (years) Premenopausal ER positive Triple negative Histology: invasive ductal carcinoma Stage at initial diagnosis Tumor grade III
41.8 56% 63–72% 9–22.4% 95%
45–49 [3] 50% [17] 52–60% [58,59] 20–22% [42,58] 88.5% [58]
SA versus non-SA: 40.5 versus 57.4 [18] 51.8 [18] 45% [19] 59–71.9% [19,20] 19 [20,44] 69.1% [19]
III–IV: 90% [37] 63%
III–IV: 60% [38] 60% [38]
III–IV: 16% [19] 41.9% [19]
III–IV: 11% [19] 34.4% [19]
62.8 [18] 24.5% [19] 70–79.3% [19,20] 8–12% [20,44] 65.6% [19]
ASR, age-standardized incidence rate; ER, estrogen receptor.
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these patients were uneducated (illiterate or having only a primary level of education) and 81% of them were housewives [15,16]. As discussed earlier, a relatively lower average age of the female population is a common phenomenon in developing countries, and therefore diagnoses of breast cancer at earlier ages are common. It is unlikely that the risk factors for premenopausal and postmenopausal breast cancer are vastly different. 4. Breast cancer detection and diagnosis None of the breast cancer cases is detected by organized screening in Bangladesh. Almost all breast cancer cases are detected clinically. Breast cancer can be detected at earlier stages by simple self-examination of the breasts [35], but most of the patients (more than 90%) seek medical attention at advanced stages: i.e., stages III and IV [15,36,37]. A prior study showed that majority of breast cancer patients presenting with a large tumor were associated with regional adenopathy, chest wall changes (often fixed to tumor or lymph nodes) and distant metastases [37]. This scenario can similarly be seen in many resource-limited countries like India [38]. In Bangladesh, general health education is poor, and few people are aware of cancer. Literature searches yielded only two reports on breast cancer knowledge and awareness among urban people of Dhaka city. One study conducted on 175 women of reproductive age showed that 41% of the participants had not even heard of breast cancer. About 94% of them mentioned that breast cancer is not a disease of old age [39]. This perception might have been acquired from the fact that the majority of the breast cancer cases in Bangladesh occur at a relatively young (premenopausal) age. Most of the respondents (about 77%) were unaware of breast cancer screening methods and more than 96% of them were unfamiliar with breast selfexamination [39]. It is encouraging, however, that nearly 92% of the women interviewed would not hesitate to seek medical help from a physician when there are problems associated with their breast [39]. Another survey – conducted mostly on educated (65% > 12 years of school) women, with 50% representing faculty members of a university – has shown that higher education is positively correlated with breast cancer screening practices and awareness [40]. Because of the low level of awareness in the population, the appearance of a mass or visible sore is usually considered non-life-threatening at the initial stage of breast cancer and is ignored. Moreover, other factors – including the high cost of treatment, fear of social stigmatization, inadequate diagnostic facilities, and lack of trust in existing healthcare systems – might be barriers to women’s decisions to seek medical help. 5. Pathologic characteristics of breast cancer In Bangladesh, approximately 95% of all breast cancers are invasive ductal carcinomas [15,41], and over 63% of the patients (n = 987) had grade III tumors [41]. Data on breast cancer markers – including estrogen receptor (ER) and progesterone receptor (PR) and Her-2/neu expression – are scarce. None of the public hospitals, including specialized NIRCH, have the marker testing facilities. Only three private clinics/hospitals offer breast cancer marker testing services, mainly for affluent people. A retrospective study on 1042 cases demonstrated that 69% and 73% of the cases were ER- and PR-positive, respectively. About 28% of 335 cases showed Her-2/neu overexpression. Only 9% of patients had triplenegative breast cancer (TNBC) [41]. There was a strong correlation between ER and PR status, whereas the expression of Her-2/neu had an inverse relationship with hormonal receptor status. Approximately 40% of grade III tumors were ER/PR-positive [41]. Interestingly, the expression of tumor markers was not correlated with the patient’s age at diagnosis. In addition, our unpublished
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data extracted from two private hospitals revealed that 62.7% of all cases (42/67) were ER-positive, while 22.4% were triple-negative. A recent clinical trial carried out by the International Breast Cancer Research Foundation (IBCRF) demonstrated that 72% of 67 patients were ER-positive [37]. In neighboring state of India (West Bengal), about 57% of breast cancer patients were ER-positive, while 22% of the cases were triple-negative [42]. The status of breast cancer hormone receptors/molecular subtypes may be influenced by race, age, grade and stage [20,43,44]. In general, the ER-positive rates in Western countries are around 70% compared with 60% in Asia [45]. The risk of triple-negative breast cancer is three times greater in women of African origin [43]. Among South Asians/Bangladeshis in the UK and US, the proportion of hormone-receptor-negative breast cancer is higher than in Caucasians (Table 1). The prevalence of TNBC was found to be the second highest in South Asians (19%) after Black women (25%) [20,44]. All these data suggest that the hormone receptor status of the South Asian population is not vastly different from that in high-income countries. 6. Breast cancer treatment Bangladesh, burdened with a huge population, is facing a severe shortage of human resources for health. There are approximately five physicians and two nurses available for every 10,000 people [46]. No national health insurance system exists in Bangladesh. While over 70% of the population live in rural areas [4], most of the secondary and tertiary healthcare facilities are centered in urban areas. Public hospitals are generally overcrowded and lack basic resources, including equipment and essential drugs. In contrast, private clinics and hospitals are relatively well equipped, but these are financially out of reach for most Bangladeshis. The recordkeeping system for the patients of both private and public hospitals are often incomplete and unsystematic. There are only two specialized hospitals (one private) dedicated to cancer treatment in Bangladesh. In addition, 14 oncology units of public medical teaching hospitals and a few private hospitals also provide services, including diagnosis and treatment for all cancer patients in the country. As there are no nationally applicable standard protocols or guidelines for managing breast cancer in Bangladesh, the quality of treatment varies widely. Only a few patients have the opportunity to get treatment at well-equipped private hospitals that use international standard protocols. In addition, affluent people often prefer to travel to neighboring countries – including Singapore, Thailand and India – to seek high-quality treatment. Compromises are made at every step in breast cancer care, including the appropriate diagnosis, surgical treatment and multi-modal therapy, considering various factors such as financial ability, tolerance and nutritional status of the patients. To ensure quality care for breast cancer patients, multidisciplinary efforts are prerequisites and require a team consisting of a pathologist, (plastic) surgeon, radiologist, radiation and medical oncologists, oncology nurses, and counselors. However, such multidisciplinary teams are not available in all hospitals. In Bangladesh, there are around 120 oncologists who offer both radiation and medical oncology services [47]. As recommended by the International Atomic Energy Agency (IAEA), Bangladesh needs at least 300 radiotherapy centers (two per 1 million of the population) for the treatment of all cancer patients. However, there are only 14 functional radiotherapy centers (nine public and five private) available in the country at the moment, and these are of varying quality. In total, 12 cobalt-60 teletherapy and nine dualenergy linear accelerator machines are currently available in those radiotherapy centers [48]. Approximately 500 hospital beds are devoted to cancer patients all over the country, which are very much insufficient for current and future needs [13].
Please cite this article in press as: Hossain MS, et al. Breast cancer in South Asia: A Bangladeshi perspective. Cancer Epidemiology (2014), http://dx.doi.org/10.1016/j.canep.2014.08.004
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A majority of patients undergo inappropriate or incomplete surgical excision at the district or community level before they are referred to a specialist. One report showed that approximately 60% of 1116 breast cancer patients underwent mastectomy or lumpectomy surgery before being admitted to the specialized cancer hospital [15]. Another study conducted in a teaching medical hospital also revealed that nearly 25% of the patients had undergone lumpectomy with no histopathological examination of removed tissues, and no additional treatments [37]. Generally, post-mastectomy reconstruction is neither recommended to nor accepted by patients due to financial burden. Breast conservation surgery is rarely practiced in Bangladesh. For the treatment of breast cancer, a wide variety of chemotherapy regimens is practiced in Bangladesh. Medical oncologists prescribe both locally manufactured generic and exported anticancer drugs for treatment. Therefore, the cost for first-line chemotherapy treatment is highly variable, ranging from BDT 10,000 [US$129; 1 US$ = 77 Bangladeshi taka (BDT)] to over BDT 15 lac (US$19,480). However, the actual outcome and effectiveness of these different chemotherapy regimens are mostly unknown as there are no scientific reports published on this aspect. If we consider other costs relating to diagnosis, surgery, specialist fee, hospital charges and transportation, the total cost is enormous, which is unbearable for the general Bangladeshi population. Palliative cancer care management for breast cancer is mostly unheard of in Bangladesh. 7. Future directions In low-income countries, the general population as well as healthcare staff are mostly unaware of the importance of screening for early detection of breast cancer and its improved treatment outcomes. In addition, medical personnel have no experience with detection and diagnosis. Access to anticancer drugs is also inadequate. From this perspective, most people consider cancer as a death sentence. Massive awareness campaigns and access programs are essential to educate communities that cancer is not inevitably a death sentence and that the risk of dying from breast cancer can be minimized significantly through screening and healthy lifestyles. For the early detection of asymptomatic breast cancer, mammography screening is widely practiced in developed countries. Although early detection is often associated with over-diagnosis (false positives), mammography screening reduces breast cancer mortality by 19% (32% for women in their 60s and nearly 15% for women in their 40s) [49]. According to the WHO, at least 70% of participants of a target population is necessary to achieve a significant reduction in mortality. Mammography screening is not economically feasible in low-income countries, including Bangladesh [50]. The National Comprehensive Cancer Network (NCCN) has recommended clinical down-staging programs such as screening by clinical breast examination (CBE) and breast selfexamination (BSE) for developing countries [51]. Recent studies in Sudan and Malaysia showed that CBE was effective in detecting early stages of breast cancer. A Malaysian study has shown that stage III– IV breast tumors could be reduced from 77% to 37% through raising public awareness and training of health workers [52]. A Sudanese study demonstrated that non-medical female volunteers from the local community could be instrumental for the implementation of a breast cancer screening program in rural areas [53]. 7.1. Female-oriented community-based healthcare approach for the prevention of breast cancer To fight against breast cancer in developing countries like Bangladesh, we need an innovative and cost-effective public health strategy, customized to local conditions, that reaches large
numbers of women, and that addresses public awareness, early detection, effective treatment and palliative care. This approach must be integrated into the existing healthcare system to make use of the limited resources in developing countries, as opposed to setting up a parallel health service solely for cancer. In conservative societies of South Asia, women are often hesitant about discussing breast-related problems in front of male health professionals. Breast cancer screening programs involving male health staff would therefore not be appropriate for either women or their husbands. In the case of Bangladesh, the existing country-wide network of community-based primary healthcare infrastructure would be very useful for raising breast cancer awareness and early detection. Female community health workers are the key to Bangladesh’s miraculous health revolution in recent years [54,55]. In 2012 there were about 219,000 female community health workers, of which 163,000 were contributed by NGOs [54]. For instance, BRAC – the world’s largest NGO – contributes over 105,000 community-based trained female health workers (known as Shasthya Shebikas), and operates in more than 65,000 (out of 84,000) villages in Bangladesh to provide a range of essential healthcare services to their communities. These healthcare workers are the key component of the well-known DOTS (directly observed treatment, shortcourse) program for effective tuberculosis control in Bangladesh [54]. The Shasthya Shebikas are recruited from local communities through a meticulous selection process. They work on a voluntary basis but receive performance-based incentives from the sale of health commodities [54,56]. Routine and systematic home visits are the cornerstone of community health programs in Bangladesh. BRAC’s female health workers visit about 25 million households every month [55]. This huge female-oriented primary healthcare infrastructure could play a vital role in cancer awareness, screening and early detection of breast cancer in Bangladesh. In conjunction with screening programs, an effective referral system must be established for those women who are being detected with breast cancer. Moreover, BRAC’s primary healthcare model system could significantly contribute to the implementation of the Kerala’s (India) community-based palliative care system in Bangladesh [57]. In fact, BRAC’s model of a primary healthcare service could be an effective tool for the prevention of breast cancer in low-income countries. 8. Specific recommendations 1. Epidemiological and strategic information are the prerequisites for setting up public health priority among the general population and at the policy level. Unfortunately, such information is lacking in Bangladesh. Multidisciplinary collaborative research initiatives addressing biological and sociological aspects are required for effective breast cancer care. 2. Breast cancer awareness and access programs need to be prioritized – through innovative approaches tailored to local conditions – for the early detection of and screening for breast cancer. 3. Collaborative efforts are necessary to integrate existing community-based primary healthcare services for breast cancer management. 4. Government has to devise a strategy for cost-effective chemotherapy drugs for cancer patients. Developing countries alone cannot solve this problem without support from the international community. 5. Good referral systems and guidelines must be established for women in whom cancer is detected. 6. Effective leadership is lacking in developing countries. In fact, this is the key to establishing effective collaboration across
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health sectors and overcoming existing mismanagement and complicated bureaucratic systems.
Conflict of interest The authors declare that they have no competing interests. Authorship contribution All authors (MSH, SF, HEK) contributed significantly to analyze data and prepare this manuscript. MSH wrote the initial draft of the manuscript. Acknowledgements We would like to thank Kazi Iftekhar, MBBS, MD (Dhaka medical college, Bangladesh), Ferdous Shahriar Sayed, MBBS, MD (United Hospital Ltd, Bangladesh) and Fazlul Karim (Eli Lilly, Bangladesh) for their valuable information regarding breast cancer treatment and cost of anticancer drugs. References [1] Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. Lyon, France: International Agency for Research on Cancer, 2014, Available from http://globocaniarcfr accessed on 07.07.14. [2] Forouzanfar MH, Foreman KJ, Delossantos AM, Lozano R, Lopez AD, Murray CJ, et al. Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. Lancet 2011;378:1461–84. [3] Leong SP, Shen ZZ, Liu TJ, Agarwal G, Tajima T, Paik NS, et al. Is breast cancer the same disease in Asian and Western countries. World J Surg 2010;34:2308–24. [4] CIA. The world factbook; 2014, https://wwwciagov/library/publications/theworld-factbook/geos/bghtml/. [5] Shetty P. India faces growing breast cancer epidemic. Lancet 2012;379:992–3. [6] Moore MA, Shin HR, Curado MP, Sobue T. Establishment of an Asian Cancer Registry Network – problems and perspectives. Asian Pac J Cancer Prev 2008;9:815–32. [7] NCDIR-NCRP. Three-year population based cancer registries (India) 2009– 2011; 2013, http://wwwicmrnicin/ncrp/PBCR_Report%202009_2011/ALL_ CONTENT/ALL_PDF/Preliminary_Pagespdf. [8] WHO. Global status report on noncommunicable diseases 2010. Description of the global burden of NCDs, their risk factors and determinants;http:// wwwwhoint/nmh/publications/ncd_report_full_enpdf. 2010. [9] WHO. Life expectancy. http://appswhoint/gho/data/nodemain688?lang=en. [10] Naila K, Simeen M. Globalization, gender and poverty: Bangladeshi women workers in export and local markets. J Int Dev 2004;16:93–109. [11] Adams AM, Rabbani A, Ahmed S, Mahmood SS, Al-Sabir A, Rashid SF, et al. Explaining equity gains in child survival in Bangladesh: scale, speed, and selectivity in health and development. Lancet 2013;382:2027–37. [12] Das P, Horton R. Bangladesh: innovating for health. Lancet 2013;382:1681–2. [13] Hussain SA, Sullivan R. Cancer control in Bangladesh. Jpn J Clin Oncol 2013;43:1159–69. [14] Ghumare SS, Cunningham JE. Breast cancer trends in Indian residents and emigrants portend an emerging epidemic for India. Asian Pac J Cancer Prev 2007;8:507–12. [15] NIRCH. Cancer Registry Report National Institute of Cancer Research and Hospital 2005–07; 2009, http://whobangladeshhealthrepositoryorg/bitstream/123456789/282/1/Publication_Cancer_Registry_Reportpdf. [16] NIRCH. Cancer Registry Report National Institute of Cancer Research and Hospital 2008–2010; 2013. [17] Khokhar A. Breast cancer in India: where do we stand and where do we go. Asian Pac J Cancer Prev 2012;13:4861–6. [18] Farooq S, Coleman MP. Breast cancer survival in South Asian women in England and Wales. J Epidemiol Community Health 2005;59:402–6. [19] Kakarala M, Rozek L, Cote M, Liyanage S, Brenner DE. Breast cancer histology and receptor status characterization in Asian Indian and Pakistani women in the US – a SEER analysis. BMC Cancer 2010;10:191. [20] Telli ML, Chang ET, Kurian AW, Keegan TH, McClure LA, Lichtensztajn D, et al. Asian ethnicity and breast cancer subtypes: a study from the California Cancer Registry. Breast Cancer Res Treat 2010;127:471–8. [21] Jack RH, Davies EA, Moller H. Breast cancer incidence, stage, treatment and survival in ethnic groups in South East, England. Br J Cancer 2009;100:545–50. [22] Ghiasvand R, Adami HO, Harirchi I, Akrami R, Zendehdel K. Higher incidence of premenopausal breast cancer in less developed countries; myth or truth? BMC Cancer 2014;14:343. [23] NIPORT. Bangladesh Maternal Mortality and Health Care Survey 2010; 2011, http://wwwcpcuncedu/measure/publications/tr-12-87.
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[24] Institute for Health Metrics and Evaluation (IHME). The Challenge ahead: progress and setbacks in breast and cervical cancer. Seattle, WA: IHME, 2011, http://www.healthdata.org/policy-report/challenge-ahead-progress-and-setbacks-breast-and-cervical-cancer. [25] Key TJ, Verkasalo PK, Banks E. Epidemiology of breast cancer. Lancet Oncol 2001;2:133–40. [26] Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50302 women with breast cancer and 96973 women without the disease. Lancet 2002;360:187–95. [27] Collaborative Group on Hormonal Factors in Breast Cancer. Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118,964 women with breast cancer from 117 epidemiological studies. Lancet Oncol 2012;13:1141–51. [28] Reeves GK, Pirie K, Beral V, Green J, Spencer E, Bull D. Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. BMJ 2007;335:1134. [29] The Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003;362:419–27. [30] Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet 1997;350:1047–59. [31] Collaborative Group on Hormonal Factors in Breast Cancer. Alcohol, tobacco and breast cancer – collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease. Br J Cancer 2002;87:1234–45. [32] Collaborative Group on Hormonal Factors in Breast Cancer. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Lancet 2001;358:1389–99. [33] Bangladesh Bureau of Statistics (BBS). Sample vital registration system 2010;http://wwwbbsgovbd/WebTestApplication/userfiles/Image/SVRS/ SVRS-10pdf. 2011. [34] Bangladesh Demographic and Health Survey 2011;http://wwwdghsgovbd/ licts_file/images/BDHS/BDHS_2011pdf. 2012. [35] Oezaras G, Durualp E, Civelek FE, Gul B, Uensal M. Analysis of breast selfexamination training efficiency in women between 20–60 years of age in Turkey. Asian Pac J Cancer Prev 2010;11:799–802. [36] Mohiuddin M, Gafur MA, Karim MR, Khan SA, Hoque MM, Islam MS, et al. Clinicopathological stages of carcinoma breast patient. Mymensingh Med J 2012;21:238–45. [37] Story HL, Love RR, Salim R, Roberto AJ, Krieger JL, Ginsburg OM. Improving outcomes from breast cancer in a low-income country: lessons from Bangladesh. Int J Breast Cancer 2012;2012:423562. [38] Agarwal G, Pradeep PV, Aggarwal V, Yip CH, Cheung PS. Spectrum of breast cancer in Asian women. World J Surg 2007;31:1031–40. [39] Chowdhury S, Sultana S. Awareness on Breast Cancer among the Women of Reproductive Age. J Family Reprod Health 2011;5:125–32. [40] Rasu RS, Rianon NJ, Shahidullah SM, Faisel AJ, Selwyn BJ. Effect of educational level on knowledge and use of breast cancer screening practices in Bangladeshi women. Health Care Women Int 2011;32:177–89. [41] Motafa MG, Larsen MT, Love RR. Estrogen receptor, progesterone receptor, and Her-2/neu oncogene expression in breast cancers among Bangladeshi women. J Bangladesh Coll Phys Surg 2010;28:157–62. [42] Jana D, Mandal S, Mukhopadhyay M, Mitra D, Mukhopadhyay SK, Sarkar DK. Prognostic significance of HER-2/neu and survival of breast cancer patients attending a specialized breast clinic in Kolkata, Eastern India. Asian Pac J Cancer Prev 2012;13:3851–5. [43] Boyle P. Triple-negative breast cancer: epidemiological considerations and recommendations. Ann Oncol 2012;23(Suppl. (6)):vi7–12. [44] Jack RH, Davies EA, Renshaw C, Tutt A, Grocock MJ, Coupland VH, et al. Differences in breast cancer hormone receptor status in ethnic groups: a London population. Eur J Cancer 2013;49:696–702. [45] Yip CH. Breast cancer in Asia. Methods Mol Biol 2009;471:51–64. [46] Ahmed SM, Hossain MA, Rajachowdhury AM, Bhuiya AU. The health workforce crisis in Bangladesh: shortage, inappropriate skill-mix and inequitable distribution. Hum Resour Health 2011;9:3. [47] Uddin AK, Khan ZJ, Islam J, Mahmud AM. Cancer care scenario in Bangladesh. South Asian J Cancer 2013;2:102–4. [48] Dirac database I. http://www-naweb.iaea.org/nahu/dirac/query1.asp?lstRegion=16. [49] Pace LE, Keating NL. A systematic assessment of benefits and risks to guide breast cancer screening decisions. JAMA 2014;311:1327–35. [50] Harford JB. Breast-cancer early detection in low-income and middle-income countries: do what you can versus one size fits all. Lancet Oncol 2011;12:306–12. [51] Anderson BO. Understanding social obstacles to early breast cancer detection is critical to improving breast cancer outcome in low- and middle-resource countries. Cancer 2010;116:4436–9. [52] Devi BC, Tang TS, Corbex M. Reducing by half the percentage of late-stage presentation for breast and cervix cancer over 4 years: a pilot study of clinical downstaging in Sarawak, Malaysia. Ann Oncol 2007;18:1172–6. [53] Abuidris DO, Elsheikh A, Ali M, Musa H, Elgaili E, Ahmed AO, et al. Breastcancer screening with trained volunteers in a rural area of Sudan: a pilot study. Lancet Oncol 2013;14:363–70.
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[54] Ahmed SM, Evans TG, Standing H, Mahmud S. Harnessing pluralism for better health in Bangladesh. Lancet 2013;382:1746–55. [55] El Arifeen S, Christou A, Reichenbach L, Osman FA, Azad K, Islam KS, et al. Community-based approaches and partnerships: innovations in healthservice delivery in Bangladesh. Lancet 2013;382:2012–26. [56] Ahmed SM. Taking healthcare where the community is: the story of the Shasthya Sebikas of BRAC in Bangladesh. BRAC Univ J 2008;1:39–45.
[57] Bollini P, Venkateswaran C, Sureshkumar K. Palliative care in Kerala, India: a model for resource-poor settings. Onkologie 2004;27:138–42. [58] Patil VW, Singhai R, Patil AV, Gurav PD. Triple-negative (ER, PgR, HER-2/neu) breast cancer in Indian women. Breast Cancer (Dove Med Press) 2011;3:9–19. [59] Rajan G, Culas TB, Jayalakshmy PS. Estrogen and progesterone receptor status in breast cancer: a cross-sectional study of 450 women in Kerala, South India. World J Surg Oncol 2014;12:120.
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Contents lists available at ScienceDirect
Cancer Epidemiology The International Journal of Cancer Epidemiology, Detection, and Prevention journal homepage: www.cancerepidemiology.net
Review
Breast cancer in South Asia: A Bangladeshi perspective Mohammad Sorowar Hossain a,d,*, Shameema Ferdous b, Henrike E. Karim-Kos c a
BRAC University, Department of Mathematical and Natural Sciences, Dhaka, Bangladesh University of Dhaka, Bangladesh c Department of Public Health, Erasmus MC University Medical Centre, Rotterdam, The Netherlands d Biotechnology Division, Incepta Pharmaceutical Ltd, Dhaka, Bangladesh b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 1 May 2014 Received in revised form 13 July 2014 Accepted 3 August 2014 Available online xxx
South Asian countries are facing a hidden breast cancer epidemic. A significant proportion of the breast cancer cases occur in premenopausal women. Knowledge of the various aspects of breast cancer in different geographical regions is limited in South Asia. In this article, we review the Bangladeshi perspective of the epidemiology, risk factors, pathology, diagnosis and treatment of breast cancer. As in other developing countries, because of the lack of breast cancer awareness in Bangladeshi population and inadequate access to health care, most patients are diagnosed at an advanced stage of the disease. Early detection has a crucial impact on overall treatment outcomes. To battle against breast cancer in resource-limited countries like Bangladesh, it is not feasible to set up a parallel health service system solely dedicated to cancer. Therefore, a cost-effective public health strategy is needed which could reach a large number of women in the country. Considering all these issues, we propose an innovative femalebased primary healthcare approach focused on awareness, screening and early detection of breast cancer in Bangladesh. This preventive strategy could be a model for other resource-limited developing countries. ß 2014 Elsevier Ltd. All rights reserved.
Keywords: Breast Bangladesh Cancer Awareness Primary healthcare South Asia Epidemiology
1. Introduction Breast cancer is the most common cancer in women worldwide. Even though the incidence of breast cancer in developing countries is lower that in their Western counterparts, it is rising rapidly. According to GLOBOCAN estimates, more than half (52.9%) of 1.67 million new breast cancer cases were diagnosed in developing countries in 2012 [1], while the corresponding figure for 1980 was only 35% [2]. Although in developed countries breast cancer is mainly a disease of postmenopausal women (50 years), almost half of all breast cancer cases (45%) in developing countries in 2010 were diagnosed in women of reproductive age (15–49 years) [2]. In Asia, the incidence of breast cancer peaks among premenopausal women in their forties, whereas among postmenopausal women in Western countries it peaks in their sixties [3]. The mortality of breast cancer is significantly higher in developing countries than in high-income countries. In 2012 nearly 62% of deaths associated with breast cancer occurred in developing countries [1].
* Corresponding author at: Department of Mathematics and Natural Sciences, BRAC University, 66 Mohakhali, Dhaka 1212, Bangladesh. Tel.: +880 2 8824051 4x4080; fax: +880 2 8810383. E-mail address: [email protected] (M.S. Hossain).
South Asia, the home of approximately 588 million women over 15 years of age [4], faces a growing breast cancer epidemic, as the incidence of breast cancer is increasing dramatically [5]. Information concerning the epidemiology, biology, and different environmental backgrounds of breast cancer are scarce in South Asia. None of the South Asian countries have central cancer registries which could provide comprehensive nationwide data. All populationbased epidemiological data in this region have been obtained from 25 Indian population-based cancer registries (that cover only 7.5% of the total Indian population) and a single Pakistani cancer registry (coverage 1%) [6,7]. An estimate of over 200,000 new breast cancer cases occurred in South Asia in 2012, and approximately 97,500 breast cancer patients died [1]. Currently breast cancer has overtaken cervical cancer as the most common cancer in South Asian women [1]. Despite current or future efforts, increases in breast cancer incidence in developing countries are expected because of the increasing lifespan resulting from efficient management of infectious diseases, and increasing adaptation to a Westernized life style [8]. With a population of over 163 million, Bangladesh is one of the most densely populated countries in the world [4]. Females have outnumbered males (84.1 versus 79.5 million) in the Bangladeshi population. About 45 million women are at reproductive age, while 13.5 million women are 50 years old [4]. As in other South
http://dx.doi.org/10.1016/j.canep.2014.08.004 1877-7821/ß 2014 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Hossain MS, et al. Breast cancer in South Asia: A Bangladeshi perspective. Cancer Epidemiology (2014), http://dx.doi.org/10.1016/j.canep.2014.08.004
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Asian countries, the life expectancy of Bangladeshi women has increased significantly in recent years from 59 years in 1990 to 70 years in 2011 [9]. Women are the key drivers of the Bangladesh economy and of its social transformation through their enormous contribution in the clothing industries [10] and in microcredit- and microfinance-based development programs [11]. Healthy women are vital for healthy families and communities. However, women’s problems generally get a lower priority in Bangladeshi society. Although Bangladesh has made enormous progress in the healthcare sector – especially related to infectious diseases, as recently highlighted by Lancet [12] – the issue of cancer is given lower priority at both policy and research levels [13]. In this review, we aim to present the current scenario of breast cancer in Bangladesh and suggest a primary healthcare-based innovative strategy for the prevention of breast cancer that could be a model for other low-income countries as well. 2. Epidemiology of breast cancer in Bangladesh Not much information on breast cancer in Bangladesh is available. So far no effort has been made toward creating population-based cancer registries or a central cancer registry to provide comprehensive nationwide data. Therefore, the incidence and prevalence of breast cancer is mostly unknown. However, according to GLOBOCAN estimates based on the extrapolation of Indian data, 14,836 new breast cancer cases were diagnosed in 2012, with an age-standardized incidence rate (ASR) of 21.4 per 100,000 [1]. This figure is likely to be an underestimate since many cases are missed due to lack of awareness, low level of education, misconceptions, poor socioeconomic status, insufficient access to health care, and poor governance. In West Bengal, India (which has a similar culture and population structure), the incidence of breast cancer is similar to that in Bangladesh (ASR 25.2 per 100,000) [14]. The only hospital-based cancer registry tracks new cancer cases systematically in Bangladesh at the National Institute of Cancer Research and Hospital (NICRH). According to an NICRH report, 5255 breast cancer cases were diagnosed during the period 2005– 2010; the mean age of the breast cancer patients was 41.8 years (age range 15–94 years) and over 56% of the cases were women of reproductive age (15–44 years) [15,16]. Similarly, in our neighboring country (India), premenopausal patients constitute about 50% of all breast cancer patients [17]. The higher proportion of premenopausal cases in Bangladesh might be due to the fact that the overall population is much younger than in high-income countries, and possibly missing cases of older women who often feel shy about seeking medical help as well as getting lower priority for treatment compared to younger family members in South Asian countries. The same pattern of a higher proportion of premenopausal cases was also seen among South Asian immigrants in the UK and US [18–20], although the incidence is significantly higher compared to women in their country of origin
(Table 1) [14,21]. A recent study has shown that the age-specific incidence rate of breast cancer is significantly lower in low-income countries (LICs) than in high-income countries (HICs). The incidence of premenopausal cases is about twice as high in HICs (ASR 29.4 versus 12.8 per 100,000) as LICs, whereas the incidence of postmenopausal cases is five-fold higher in HICs (307.6 versus 65.5 per 100,000) [22]. Hence, it has been suggested that the global differences in incidence rate of breast cancer are likely due to the differences in the level of exposures to various reproductive and lifestyle risk factors [22]. Since there is no national registry of cause of death in Bangladesh or of patients’ follow-up systems in hospitals, it is not possible to know about the mortality and survivorship of breast cancer. Nonetheless, GLOBOCAN has estimated that 7142 women died of breast cancer in Bangladesh in 2012 (ASR 11 per 100,000) [1]. Apart from this, a maternal health survey estimated that cancer was responsible for 21% of all women’s deaths in the reproductive age range [23]. Another verbal autopsy study showed that 62% of all deaths associated with breast cancer were in women under 50 years old [24]. 3. Risk factors Some reproductive factors (age at menarche, menopause and first pregnancy, breastfeeding, parity) and non-reproductive factors (menopausal hormone therapy, family history of cancer, body mass index, alcohol intake, and others) have been linked with breast cancer risk [25]. Compelling evidence suggests that certain factors are known to reduce the risk of breast cancer, including increased parity and duration of breastfeeding [26], older age at menarche [27], and lower body mass index [28]. In contrast, use of menopausal hormone therapy [29,30], greater alcohol consumption [31], older age at menopause [27], and a positive family history [32] are known to increase the risk of breast cancer. No case–control studies have been conducted on breast cancer risk factors in the environmental context of Bangladesh. However, well known reproductive factors may not be strongly associated with the breast cancer burden in Bangladesh, where the majority of breast cancer cases are premenopausal. Marriage at an early age, breastfeeding for a longer period of time, and multiple births are the common features in Bangladeshi society. For females, the mean age at first marriage is 18.7 years [33]. Almost all Bangladeshi babies are breastfed for the first year of life, and 90% of these children receive breast milk until the age of 20–23 months [34]. Data from the NICRH cancer registry show that over 93% of all breast cancer patients (n = 5255) were married. Altogether, over 78% of them were multiparous (having given birth two or more times; 56%) and grand multiparous (having given birth five or more times; approximately 22%) [15,16]. In contrast, only about 9% of the cases were nulliparous. Most of the female patients registered at NICRH came from poor family backgrounds since nearly 80% of
Table 1 Characteristics of breast cancer in Bangladesh as compared to other countries. Features
Bangladesh
India
South Asian (SA) immigrant in UK/US
UK/US
Incidence (ASR per 100,000)
21.4
25.8[1]
95 in UK, 92.9 in US [1]
Mean age (years) Premenopausal ER positive Triple negative Histology: invasive ductal carcinoma Stage at initial diagnosis Tumor grade III
41.8 56% 63–72% 9–22.4% 95%
45–49 [3] 50% [17] 52–60% [58,59] 20–22% [42,58] 88.5% [58]
SA versus non-SA: 40.5 versus 57.4 [18] 51.8 [18] 45% [19] 59–71.9% [19,20] 19 [20,44] 69.1% [19]
III–IV: 90% [37] 63%
III–IV: 60% [38] 60% [38]
III–IV: 16% [19] 41.9% [19]
III–IV: 11% [19] 34.4% [19]
62.8 [18] 24.5% [19] 70–79.3% [19,20] 8–12% [20,44] 65.6% [19]
ASR, age-standardized incidence rate; ER, estrogen receptor.
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these patients were uneducated (illiterate or having only a primary level of education) and 81% of them were housewives [15,16]. As discussed earlier, a relatively lower average age of the female population is a common phenomenon in developing countries, and therefore diagnoses of breast cancer at earlier ages are common. It is unlikely that the risk factors for premenopausal and postmenopausal breast cancer are vastly different. 4. Breast cancer detection and diagnosis None of the breast cancer cases is detected by organized screening in Bangladesh. Almost all breast cancer cases are detected clinically. Breast cancer can be detected at earlier stages by simple self-examination of the breasts [35], but most of the patients (more than 90%) seek medical attention at advanced stages: i.e., stages III and IV [15,36,37]. A prior study showed that majority of breast cancer patients presenting with a large tumor were associated with regional adenopathy, chest wall changes (often fixed to tumor or lymph nodes) and distant metastases [37]. This scenario can similarly be seen in many resource-limited countries like India [38]. In Bangladesh, general health education is poor, and few people are aware of cancer. Literature searches yielded only two reports on breast cancer knowledge and awareness among urban people of Dhaka city. One study conducted on 175 women of reproductive age showed that 41% of the participants had not even heard of breast cancer. About 94% of them mentioned that breast cancer is not a disease of old age [39]. This perception might have been acquired from the fact that the majority of the breast cancer cases in Bangladesh occur at a relatively young (premenopausal) age. Most of the respondents (about 77%) were unaware of breast cancer screening methods and more than 96% of them were unfamiliar with breast selfexamination [39]. It is encouraging, however, that nearly 92% of the women interviewed would not hesitate to seek medical help from a physician when there are problems associated with their breast [39]. Another survey – conducted mostly on educated (65% > 12 years of school) women, with 50% representing faculty members of a university – has shown that higher education is positively correlated with breast cancer screening practices and awareness [40]. Because of the low level of awareness in the population, the appearance of a mass or visible sore is usually considered non-life-threatening at the initial stage of breast cancer and is ignored. Moreover, other factors – including the high cost of treatment, fear of social stigmatization, inadequate diagnostic facilities, and lack of trust in existing healthcare systems – might be barriers to women’s decisions to seek medical help. 5. Pathologic characteristics of breast cancer In Bangladesh, approximately 95% of all breast cancers are invasive ductal carcinomas [15,41], and over 63% of the patients (n = 987) had grade III tumors [41]. Data on breast cancer markers – including estrogen receptor (ER) and progesterone receptor (PR) and Her-2/neu expression – are scarce. None of the public hospitals, including specialized NIRCH, have the marker testing facilities. Only three private clinics/hospitals offer breast cancer marker testing services, mainly for affluent people. A retrospective study on 1042 cases demonstrated that 69% and 73% of the cases were ER- and PR-positive, respectively. About 28% of 335 cases showed Her-2/neu overexpression. Only 9% of patients had triplenegative breast cancer (TNBC) [41]. There was a strong correlation between ER and PR status, whereas the expression of Her-2/neu had an inverse relationship with hormonal receptor status. Approximately 40% of grade III tumors were ER/PR-positive [41]. Interestingly, the expression of tumor markers was not correlated with the patient’s age at diagnosis. In addition, our unpublished
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data extracted from two private hospitals revealed that 62.7% of all cases (42/67) were ER-positive, while 22.4% were triple-negative. A recent clinical trial carried out by the International Breast Cancer Research Foundation (IBCRF) demonstrated that 72% of 67 patients were ER-positive [37]. In neighboring state of India (West Bengal), about 57% of breast cancer patients were ER-positive, while 22% of the cases were triple-negative [42]. The status of breast cancer hormone receptors/molecular subtypes may be influenced by race, age, grade and stage [20,43,44]. In general, the ER-positive rates in Western countries are around 70% compared with 60% in Asia [45]. The risk of triple-negative breast cancer is three times greater in women of African origin [43]. Among South Asians/Bangladeshis in the UK and US, the proportion of hormone-receptor-negative breast cancer is higher than in Caucasians (Table 1). The prevalence of TNBC was found to be the second highest in South Asians (19%) after Black women (25%) [20,44]. All these data suggest that the hormone receptor status of the South Asian population is not vastly different from that in high-income countries. 6. Breast cancer treatment Bangladesh, burdened with a huge population, is facing a severe shortage of human resources for health. There are approximately five physicians and two nurses available for every 10,000 people [46]. No national health insurance system exists in Bangladesh. While over 70% of the population live in rural areas [4], most of the secondary and tertiary healthcare facilities are centered in urban areas. Public hospitals are generally overcrowded and lack basic resources, including equipment and essential drugs. In contrast, private clinics and hospitals are relatively well equipped, but these are financially out of reach for most Bangladeshis. The recordkeeping system for the patients of both private and public hospitals are often incomplete and unsystematic. There are only two specialized hospitals (one private) dedicated to cancer treatment in Bangladesh. In addition, 14 oncology units of public medical teaching hospitals and a few private hospitals also provide services, including diagnosis and treatment for all cancer patients in the country. As there are no nationally applicable standard protocols or guidelines for managing breast cancer in Bangladesh, the quality of treatment varies widely. Only a few patients have the opportunity to get treatment at well-equipped private hospitals that use international standard protocols. In addition, affluent people often prefer to travel to neighboring countries – including Singapore, Thailand and India – to seek high-quality treatment. Compromises are made at every step in breast cancer care, including the appropriate diagnosis, surgical treatment and multi-modal therapy, considering various factors such as financial ability, tolerance and nutritional status of the patients. To ensure quality care for breast cancer patients, multidisciplinary efforts are prerequisites and require a team consisting of a pathologist, (plastic) surgeon, radiologist, radiation and medical oncologists, oncology nurses, and counselors. However, such multidisciplinary teams are not available in all hospitals. In Bangladesh, there are around 120 oncologists who offer both radiation and medical oncology services [47]. As recommended by the International Atomic Energy Agency (IAEA), Bangladesh needs at least 300 radiotherapy centers (two per 1 million of the population) for the treatment of all cancer patients. However, there are only 14 functional radiotherapy centers (nine public and five private) available in the country at the moment, and these are of varying quality. In total, 12 cobalt-60 teletherapy and nine dualenergy linear accelerator machines are currently available in those radiotherapy centers [48]. Approximately 500 hospital beds are devoted to cancer patients all over the country, which are very much insufficient for current and future needs [13].
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A majority of patients undergo inappropriate or incomplete surgical excision at the district or community level before they are referred to a specialist. One report showed that approximately 60% of 1116 breast cancer patients underwent mastectomy or lumpectomy surgery before being admitted to the specialized cancer hospital [15]. Another study conducted in a teaching medical hospital also revealed that nearly 25% of the patients had undergone lumpectomy with no histopathological examination of removed tissues, and no additional treatments [37]. Generally, post-mastectomy reconstruction is neither recommended to nor accepted by patients due to financial burden. Breast conservation surgery is rarely practiced in Bangladesh. For the treatment of breast cancer, a wide variety of chemotherapy regimens is practiced in Bangladesh. Medical oncologists prescribe both locally manufactured generic and exported anticancer drugs for treatment. Therefore, the cost for first-line chemotherapy treatment is highly variable, ranging from BDT 10,000 [US$129; 1 US$ = 77 Bangladeshi taka (BDT)] to over BDT 15 lac (US$19,480). However, the actual outcome and effectiveness of these different chemotherapy regimens are mostly unknown as there are no scientific reports published on this aspect. If we consider other costs relating to diagnosis, surgery, specialist fee, hospital charges and transportation, the total cost is enormous, which is unbearable for the general Bangladeshi population. Palliative cancer care management for breast cancer is mostly unheard of in Bangladesh. 7. Future directions In low-income countries, the general population as well as healthcare staff are mostly unaware of the importance of screening for early detection of breast cancer and its improved treatment outcomes. In addition, medical personnel have no experience with detection and diagnosis. Access to anticancer drugs is also inadequate. From this perspective, most people consider cancer as a death sentence. Massive awareness campaigns and access programs are essential to educate communities that cancer is not inevitably a death sentence and that the risk of dying from breast cancer can be minimized significantly through screening and healthy lifestyles. For the early detection of asymptomatic breast cancer, mammography screening is widely practiced in developed countries. Although early detection is often associated with over-diagnosis (false positives), mammography screening reduces breast cancer mortality by 19% (32% for women in their 60s and nearly 15% for women in their 40s) [49]. According to the WHO, at least 70% of participants of a target population is necessary to achieve a significant reduction in mortality. Mammography screening is not economically feasible in low-income countries, including Bangladesh [50]. The National Comprehensive Cancer Network (NCCN) has recommended clinical down-staging programs such as screening by clinical breast examination (CBE) and breast selfexamination (BSE) for developing countries [51]. Recent studies in Sudan and Malaysia showed that CBE was effective in detecting early stages of breast cancer. A Malaysian study has shown that stage III– IV breast tumors could be reduced from 77% to 37% through raising public awareness and training of health workers [52]. A Sudanese study demonstrated that non-medical female volunteers from the local community could be instrumental for the implementation of a breast cancer screening program in rural areas [53]. 7.1. Female-oriented community-based healthcare approach for the prevention of breast cancer To fight against breast cancer in developing countries like Bangladesh, we need an innovative and cost-effective public health strategy, customized to local conditions, that reaches large
numbers of women, and that addresses public awareness, early detection, effective treatment and palliative care. This approach must be integrated into the existing healthcare system to make use of the limited resources in developing countries, as opposed to setting up a parallel health service solely for cancer. In conservative societies of South Asia, women are often hesitant about discussing breast-related problems in front of male health professionals. Breast cancer screening programs involving male health staff would therefore not be appropriate for either women or their husbands. In the case of Bangladesh, the existing country-wide network of community-based primary healthcare infrastructure would be very useful for raising breast cancer awareness and early detection. Female community health workers are the key to Bangladesh’s miraculous health revolution in recent years [54,55]. In 2012 there were about 219,000 female community health workers, of which 163,000 were contributed by NGOs [54]. For instance, BRAC – the world’s largest NGO – contributes over 105,000 community-based trained female health workers (known as Shasthya Shebikas), and operates in more than 65,000 (out of 84,000) villages in Bangladesh to provide a range of essential healthcare services to their communities. These healthcare workers are the key component of the well-known DOTS (directly observed treatment, shortcourse) program for effective tuberculosis control in Bangladesh [54]. The Shasthya Shebikas are recruited from local communities through a meticulous selection process. They work on a voluntary basis but receive performance-based incentives from the sale of health commodities [54,56]. Routine and systematic home visits are the cornerstone of community health programs in Bangladesh. BRAC’s female health workers visit about 25 million households every month [55]. This huge female-oriented primary healthcare infrastructure could play a vital role in cancer awareness, screening and early detection of breast cancer in Bangladesh. In conjunction with screening programs, an effective referral system must be established for those women who are being detected with breast cancer. Moreover, BRAC’s primary healthcare model system could significantly contribute to the implementation of the Kerala’s (India) community-based palliative care system in Bangladesh [57]. In fact, BRAC’s model of a primary healthcare service could be an effective tool for the prevention of breast cancer in low-income countries. 8. Specific recommendations 1. Epidemiological and strategic information are the prerequisites for setting up public health priority among the general population and at the policy level. Unfortunately, such information is lacking in Bangladesh. Multidisciplinary collaborative research initiatives addressing biological and sociological aspects are required for effective breast cancer care. 2. Breast cancer awareness and access programs need to be prioritized – through innovative approaches tailored to local conditions – for the early detection of and screening for breast cancer. 3. Collaborative efforts are necessary to integrate existing community-based primary healthcare services for breast cancer management. 4. Government has to devise a strategy for cost-effective chemotherapy drugs for cancer patients. Developing countries alone cannot solve this problem without support from the international community. 5. Good referral systems and guidelines must be established for women in whom cancer is detected. 6. Effective leadership is lacking in developing countries. In fact, this is the key to establishing effective collaboration across
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health sectors and overcoming existing mismanagement and complicated bureaucratic systems.
Conflict of interest The authors declare that they have no competing interests. Authorship contribution All authors (MSH, SF, HEK) contributed significantly to analyze data and prepare this manuscript. MSH wrote the initial draft of the manuscript. Acknowledgements We would like to thank Kazi Iftekhar, MBBS, MD (Dhaka medical college, Bangladesh), Ferdous Shahriar Sayed, MBBS, MD (United Hospital Ltd, Bangladesh) and Fazlul Karim (Eli Lilly, Bangladesh) for their valuable information regarding breast cancer treatment and cost of anticancer drugs. References [1] Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. Lyon, France: International Agency for Research on Cancer, 2014, Available from http://globocaniarcfr accessed on 07.07.14. [2] Forouzanfar MH, Foreman KJ, Delossantos AM, Lozano R, Lopez AD, Murray CJ, et al. Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. Lancet 2011;378:1461–84. [3] Leong SP, Shen ZZ, Liu TJ, Agarwal G, Tajima T, Paik NS, et al. Is breast cancer the same disease in Asian and Western countries. World J Surg 2010;34:2308–24. [4] CIA. The world factbook; 2014, https://wwwciagov/library/publications/theworld-factbook/geos/bghtml/. [5] Shetty P. India faces growing breast cancer epidemic. Lancet 2012;379:992–3. [6] Moore MA, Shin HR, Curado MP, Sobue T. Establishment of an Asian Cancer Registry Network – problems and perspectives. Asian Pac J Cancer Prev 2008;9:815–32. [7] NCDIR-NCRP. Three-year population based cancer registries (India) 2009– 2011; 2013, http://wwwicmrnicin/ncrp/PBCR_Report%202009_2011/ALL_ CONTENT/ALL_PDF/Preliminary_Pagespdf. [8] WHO. Global status report on noncommunicable diseases 2010. Description of the global burden of NCDs, their risk factors and determinants;http:// wwwwhoint/nmh/publications/ncd_report_full_enpdf. 2010. [9] WHO. Life expectancy. http://appswhoint/gho/data/nodemain688?lang=en. [10] Naila K, Simeen M. Globalization, gender and poverty: Bangladeshi women workers in export and local markets. J Int Dev 2004;16:93–109. [11] Adams AM, Rabbani A, Ahmed S, Mahmood SS, Al-Sabir A, Rashid SF, et al. Explaining equity gains in child survival in Bangladesh: scale, speed, and selectivity in health and development. Lancet 2013;382:2027–37. [12] Das P, Horton R. Bangladesh: innovating for health. Lancet 2013;382:1681–2. [13] Hussain SA, Sullivan R. Cancer control in Bangladesh. Jpn J Clin Oncol 2013;43:1159–69. [14] Ghumare SS, Cunningham JE. Breast cancer trends in Indian residents and emigrants portend an emerging epidemic for India. Asian Pac J Cancer Prev 2007;8:507–12. [15] NIRCH. Cancer Registry Report National Institute of Cancer Research and Hospital 2005–07; 2009, http://whobangladeshhealthrepositoryorg/bitstream/123456789/282/1/Publication_Cancer_Registry_Reportpdf. [16] NIRCH. Cancer Registry Report National Institute of Cancer Research and Hospital 2008–2010; 2013. [17] Khokhar A. Breast cancer in India: where do we stand and where do we go. Asian Pac J Cancer Prev 2012;13:4861–6. [18] Farooq S, Coleman MP. Breast cancer survival in South Asian women in England and Wales. J Epidemiol Community Health 2005;59:402–6. [19] Kakarala M, Rozek L, Cote M, Liyanage S, Brenner DE. Breast cancer histology and receptor status characterization in Asian Indian and Pakistani women in the US – a SEER analysis. BMC Cancer 2010;10:191. [20] Telli ML, Chang ET, Kurian AW, Keegan TH, McClure LA, Lichtensztajn D, et al. Asian ethnicity and breast cancer subtypes: a study from the California Cancer Registry. Breast Cancer Res Treat 2010;127:471–8. [21] Jack RH, Davies EA, Moller H. Breast cancer incidence, stage, treatment and survival in ethnic groups in South East, England. Br J Cancer 2009;100:545–50. [22] Ghiasvand R, Adami HO, Harirchi I, Akrami R, Zendehdel K. Higher incidence of premenopausal breast cancer in less developed countries; myth or truth? BMC Cancer 2014;14:343. [23] NIPORT. Bangladesh Maternal Mortality and Health Care Survey 2010; 2011, http://wwwcpcuncedu/measure/publications/tr-12-87.
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[24] Institute for Health Metrics and Evaluation (IHME). The Challenge ahead: progress and setbacks in breast and cervical cancer. Seattle, WA: IHME, 2011, http://www.healthdata.org/policy-report/challenge-ahead-progress-and-setbacks-breast-and-cervical-cancer. [25] Key TJ, Verkasalo PK, Banks E. Epidemiology of breast cancer. Lancet Oncol 2001;2:133–40. [26] Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50302 women with breast cancer and 96973 women without the disease. Lancet 2002;360:187–95. [27] Collaborative Group on Hormonal Factors in Breast Cancer. Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118,964 women with breast cancer from 117 epidemiological studies. Lancet Oncol 2012;13:1141–51. [28] Reeves GK, Pirie K, Beral V, Green J, Spencer E, Bull D. Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. BMJ 2007;335:1134. [29] The Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003;362:419–27. [30] Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet 1997;350:1047–59. [31] Collaborative Group on Hormonal Factors in Breast Cancer. Alcohol, tobacco and breast cancer – collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease. Br J Cancer 2002;87:1234–45. [32] Collaborative Group on Hormonal Factors in Breast Cancer. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Lancet 2001;358:1389–99. [33] Bangladesh Bureau of Statistics (BBS). Sample vital registration system 2010;http://wwwbbsgovbd/WebTestApplication/userfiles/Image/SVRS/ SVRS-10pdf. 2011. [34] Bangladesh Demographic and Health Survey 2011;http://wwwdghsgovbd/ licts_file/images/BDHS/BDHS_2011pdf. 2012. [35] Oezaras G, Durualp E, Civelek FE, Gul B, Uensal M. Analysis of breast selfexamination training efficiency in women between 20–60 years of age in Turkey. Asian Pac J Cancer Prev 2010;11:799–802. [36] Mohiuddin M, Gafur MA, Karim MR, Khan SA, Hoque MM, Islam MS, et al. Clinicopathological stages of carcinoma breast patient. Mymensingh Med J 2012;21:238–45. [37] Story HL, Love RR, Salim R, Roberto AJ, Krieger JL, Ginsburg OM. Improving outcomes from breast cancer in a low-income country: lessons from Bangladesh. Int J Breast Cancer 2012;2012:423562. [38] Agarwal G, Pradeep PV, Aggarwal V, Yip CH, Cheung PS. Spectrum of breast cancer in Asian women. World J Surg 2007;31:1031–40. [39] Chowdhury S, Sultana S. Awareness on Breast Cancer among the Women of Reproductive Age. J Family Reprod Health 2011;5:125–32. [40] Rasu RS, Rianon NJ, Shahidullah SM, Faisel AJ, Selwyn BJ. Effect of educational level on knowledge and use of breast cancer screening practices in Bangladeshi women. Health Care Women Int 2011;32:177–89. [41] Motafa MG, Larsen MT, Love RR. Estrogen receptor, progesterone receptor, and Her-2/neu oncogene expression in breast cancers among Bangladeshi women. J Bangladesh Coll Phys Surg 2010;28:157–62. [42] Jana D, Mandal S, Mukhopadhyay M, Mitra D, Mukhopadhyay SK, Sarkar DK. Prognostic significance of HER-2/neu and survival of breast cancer patients attending a specialized breast clinic in Kolkata, Eastern India. Asian Pac J Cancer Prev 2012;13:3851–5. [43] Boyle P. Triple-negative breast cancer: epidemiological considerations and recommendations. Ann Oncol 2012;23(Suppl. (6)):vi7–12. [44] Jack RH, Davies EA, Renshaw C, Tutt A, Grocock MJ, Coupland VH, et al. Differences in breast cancer hormone receptor status in ethnic groups: a London population. Eur J Cancer 2013;49:696–702. [45] Yip CH. Breast cancer in Asia. Methods Mol Biol 2009;471:51–64. [46] Ahmed SM, Hossain MA, Rajachowdhury AM, Bhuiya AU. The health workforce crisis in Bangladesh: shortage, inappropriate skill-mix and inequitable distribution. Hum Resour Health 2011;9:3. [47] Uddin AK, Khan ZJ, Islam J, Mahmud AM. Cancer care scenario in Bangladesh. South Asian J Cancer 2013;2:102–4. [48] Dirac database I. http://www-naweb.iaea.org/nahu/dirac/query1.asp?lstRegion=16. [49] Pace LE, Keating NL. A systematic assessment of benefits and risks to guide breast cancer screening decisions. JAMA 2014;311:1327–35. [50] Harford JB. Breast-cancer early detection in low-income and middle-income countries: do what you can versus one size fits all. Lancet Oncol 2011;12:306–12. [51] Anderson BO. Understanding social obstacles to early breast cancer detection is critical to improving breast cancer outcome in low- and middle-resource countries. Cancer 2010;116:4436–9. [52] Devi BC, Tang TS, Corbex M. Reducing by half the percentage of late-stage presentation for breast and cervix cancer over 4 years: a pilot study of clinical downstaging in Sarawak, Malaysia. Ann Oncol 2007;18:1172–6. [53] Abuidris DO, Elsheikh A, Ali M, Musa H, Elgaili E, Ahmed AO, et al. Breastcancer screening with trained volunteers in a rural area of Sudan: a pilot study. Lancet Oncol 2013;14:363–70.
Please cite this article in press as: Hossain MS, et al. Breast cancer in South Asia: A Bangladeshi perspective. Cancer Epidemiology (2014), http://dx.doi.org/10.1016/j.canep.2014.08.004
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[54] Ahmed SM, Evans TG, Standing H, Mahmud S. Harnessing pluralism for better health in Bangladesh. Lancet 2013;382:1746–55. [55] El Arifeen S, Christou A, Reichenbach L, Osman FA, Azad K, Islam KS, et al. Community-based approaches and partnerships: innovations in healthservice delivery in Bangladesh. Lancet 2013;382:2012–26. [56] Ahmed SM. Taking healthcare where the community is: the story of the Shasthya Sebikas of BRAC in Bangladesh. BRAC Univ J 2008;1:39–45.
[57] Bollini P, Venkateswaran C, Sureshkumar K. Palliative care in Kerala, India: a model for resource-poor settings. Onkologie 2004;27:138–42. [58] Patil VW, Singhai R, Patil AV, Gurav PD. Triple-negative (ER, PgR, HER-2/neu) breast cancer in Indian women. Breast Cancer (Dove Med Press) 2011;3:9–19. [59] Rajan G, Culas TB, Jayalakshmy PS. Estrogen and progesterone receptor status in breast cancer: a cross-sectional study of 450 women in Kerala, South India. World J Surg Oncol 2014;12:120.
Please cite this article in press as: Hossain MS, et al. Breast cancer in South Asia: A Bangladeshi perspective. Cancer Epidemiology (2014), http://dx.doi.org/10.1016/j.canep.2014.08.004
