Background To Breast Cancer Biology Essay

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Abstract:

Background- Breast cancer (BC) cases have been increasing worldwide over the span of last few decades, but the greatest increase is seen in developing Asian countries. In 2008 India, had about 115,000 new cases with 53,000 deaths a ratio of 2:1 (meaning 1 death for 2 detected cases). There is a lacuna in documentation of the true incidence of breast cancer in India. This retrospective study was carried out for the better understanding the socio-demographic pattern and risk factors of BC patients presenting to a tertiary care hospital, located in North Karnataka in Southern India.

Methods- The record based descriptive epidemiological data pertaining to demography and risk factors for carcinoma breast for period of 2001-10 were analyzed.

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Results- Totally 20,505 cases of cancer were reported during 2001-2010 of which 1,829 (8.92%) were BC patients. The average age was 49.16 and the median age was 48. Maximum numbers were in the age group of 41-50. Most of the patients came from rural area and majority were from lower socioeconomic status. Obesity was seen in 34.00% of patients. The most common histology was infiltrating duct carcinoma (92.07%). Family history of cancer was seen in 107 (7.19%) of cases.

Conclusions- This epidemiological study helps to know the incidence of BC in this region and to some extent the associated probable risk factors. The increasing burden of BC in Indian women warrants rigorous epidemiological investigations of trends observed in different rural, semi-urban and urban populations.

Key Words- Breast cancer, India, Epidemiology, Pattern, Profile

Introduction. This section should contain a statement regarding the purpose or aim of the study, the rationale for the study, and a brief summary of previous relevant investigations.

Introduction:

Breast cancer (BC) cases have been increasing worldwide over the span of last few decades , but the greatest increase is seen in developing Asian countries . The average age of BC in Asian women is in their forties , and the same in USA and Europe, it is in their sixties. The difference in this pattern may be associated with multiple factors, like geographic variation, racial/ethnic background, genetic variation, lifestyle, environmental factors, socioeconomic status, the presence of known risk factors, utilization of screening mammography, stage of disease at diagnosis, and the availability of appropriate care .

A comparison of BC in India with western nations like the USA gives a good idea of the trends it is following. This comparison is obtained from 'Globocon' data, the latest of which is for the year 2008. The lifetime probability of developing BC in India is 1 in 22 women compared to 1 in 8 in US and other developed countries . But if you see the actual number of cases, India is not far behind. In the year 2008, there were about 182,000 BC cases reported in the USA, whereas in India, 115,000 new cases were reported. This implies that although the percentage of incidence of BC is less the total number of cases is 2/3rd of that of USA and is steadily rising. A ratio between the incidence and mortality gives a good idea of disease management and patient survival. For USA, we have 182,000 new cases and about 40,000 deaths, a ratio of 4.5:1 (meaning about 1 death for 4.5 new cases detected). Where as in India, we have about 115,000 new cases with 53,000 deaths a ratio of 2:1 (meaning 1 death for 2 detected cases). As the management strategies and disease control programs evolve, the mortality will decrease. A later stage at diagnosis and lower survival have been linked to poor access to health care facilities and lower awareness, especially in the urban poor and rural populations as well as demographic factors such as lower education and literacy . For want of compulsory reporting of cancers, there is a lacuna in documentation of the true incidence of BC in India. Many of the BCs are treated in small hospitals and are never reported, consequently the true incidence is much higher than recorded . More emphasis should be given on early detection and increased use of systemic therapy. This can be achieved with a better understanding of the trends, age group involved with other risk factors involved in the manifestation of BC .

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Cancer in humans can be best understood at population level by epidemiological studies. Epidemiology is the study of the distribution and patterns of incidence of disease, characteristics of the disease and their causes or influences in well-defined populations. In recent years epidemiological based studies at local population based level are increasingly gaining importance. Such studies enable us to study gene-environment interactions and to assess the effects of our interventions at the population level .

BC presents a great deal of immunological and histological heterogeneity in character . There are many schools of thoughts with regard to the management of BC. Hence the knowledge of the trends and pattern for specific populations is essential. This retrospective study was carried out for the better understanding of the trend, age group involved with other risk factors among BC patients, reporting to a premier tertiary cancer care center, Karnataka Cancer Therapy and Research Center (KCTRI), located in North Karnataka in Southern India (Fig 1).

Methods. Materials and procedures should be presented in sufficient detail so that the work can be repeated by other investigators. Methods previously published should not be described in detail; rather, appropriate references should be cited.

Methods:

A retrospective and descriptive study was undertaken, covering a period of 10 years from 2001-2010. It was conducted in a hospital situated in North Karnataka in South India. This hospital is providing tertiary cancer care to patients in northern Karnataka and neighboring areas. After obtaining approval from the institutional ethical committee, the medical records department was approached to obtain case files of all the cancer cases in the period. Histopathologically diagnosed cases of BC with regular follow-up were included in the study. The data of the patients with irregular follow-up (less than six months) was excluded. A total of 1829 patients presented to the hospital, of which 1488 patients fulfilled the inclusion criteria and their data regarding age, past history and family history, etc. were retrieved and collected on a predesigned proforma. Data were tabulated and analyzed using SPSS, version 11.5, statistical analysis programme (SPSS, Inc., Chicago, IL).

Results. This section should contain a concise description of the data provided in the tables and figures, which should be readily comprehensible. Excessive explanations of the data presented in tables and figures should be avoided.

Results:

Totally 20,505 cases of cancer were reported during 2001-2010, of which 9,333 (45.5%) were males and 11,172 (54.5%) were females. Considering both the sexes the three major cancers were cervical cancer with 4,605 (22.46%) patients, esophageal cancer with 3,485 (17%) patients and oral cavity cancer with 2,509 (12.24%) patients. BC ranked fifth overall with 1,829 (8.92%) patients. Likewise in males esophageal cancer had 2,103 (22.53%) patients, pharyngeal cancer 2,071 (22.19%) patients and oral cavity cancer 1,816 (19.46%) patients. Similarly in females' major cancers were cervical cancer with 4,605 (41.22%) patients, BC with 1,795 (16.07%) patients and esophageal cancer with 1,382 (12.37%) patients (Table 1). Of the total 1,829 registered BC patients, the data of 1,488 which satisfied the inclusion criteria was used for further analysis.

Among 1,488 BC patients 1,470 (98.79%) were females and 18 (1.21%) were males. The average age of the patients was 49.16 (SD=11.79) and the median age was 48. The youngest and the oldest patients were 16 and 92 respectively. Maximum number of patients i.e. 509 (34.21%) were in the age group of 41-50, followed by 343 (23.05%) patients in the age group of 51-60 (Graph 1 and 2). 912 (61.29%) of the patients were pre-menopausal and younger than 50 years (Table 2).

Most of the patients came from rural area (70%), compared to urban (30%) area. 84.88% patients were Hindus, 13.31% were Muslims and 1.81% were Christians (Table 2). Most of patients were house wives (86.92) and a majority of the patients were found to be of lower socioeconomic status. Very few patients indulged in habits like chewing tobacco or beetlenut (3.90%). 61.30% patients followed vegetarian diet while 38.70% eat non-vegetarian food. Obesity was seen in 34.00% of patients, 15.00% were over-weight, 29.00% were of normal weight and 22.00% patients were underweight (Graph 3).

48.20% patients had a lump in the right breast and 51.35% cases had it in the left breast. 0.27% had lumps in both breasts. The most common histology was infiltrating duct carcinoma (92.07%). Family history of cancer was seen in 107 (7.19%) of cases.

Discussion. The results should be interpreted and related to existing knowledge in the field. Information already presented in the Introduction or Results sections should not be repeated.

Discussion:

The aim of this retrospective analysis was to study the epidemiology of BC at KCTRI a prominent tertiary cancer care hospital situated in North Karnataka in South India. BC accounts for about one-fourth of all cancers in Indian women and about half of all cancer-related deaths. With the exception of Chennai, all urban population- based registries in India reported BC as the most common female malignancy over the years 2000-2009. In earlier reports, cancer of the uterine cervix was the most common type of cancer, even in urban centers. BC remains second after cervical cancer as the most common female malignancy reported in Chennai's urban population-based cancer registry and in Barshi's rural population-based registry. Data from all urban and rural population-based cancer registries in India suggest a rising incidence of BC in India . Similar rates of increase in BC can be seen in the present study (Graph 4).

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Advancing age is considered to be a significant risk factor in the western literature; however women in Asia including India in particular appear to be at risk at an earlier age as is illustrated from the age distribution of the cases in this study as well . In India, BC incidence peaks among women 45-50 years of age . The mean age of women with BC in our study is 49.16 (SD=11.79) years which is younger than seen in epidemiological reports on BC elsewhere in developed countries . Other Indian studies have shown similar of lower mean age that is closer to that in the present study . Median age of 48 years in our patients with BC is much lower than median age seen in American population at 62 years . This shows that Indian population has lower age at presentation in contrast to the western population and calls for having different recommendations of screening age .

Much of the increase of BC in India has been associated with greater urbanization and changing life styles. The population in this study was predominantly from a rural background. This reaffirms the fact that this disease is no longer confined to an urban setting . Out of all the patients 70% were from a rural background. However, other reports from India as well as United States show higher incidence in urban population compared to the rural population . The difference is possibly due to the fact that women in rural areas face substantial barriers in receiving preventive health care services . However, KCTRI caters to maximum patients from rural area, thus accounting for higher number of rural breast carcinoma patients. Furthermore, the consolidated report of the Indian Council of Medical Research (ICMR) on Population Based Cancer Registry (PBCR) cites that 70-80% of India's population resides in rural areas and the currently available data is mainly from the urban registries, therefore, to estimate the load of cancer is difficult . A majority of the patients were found to be of lower socioeconomic status and a similar finding has been observed in other studies .

The most remarkable feature of the Indian population structure is the clear division of its population into strictly defined endogamous castes, tribes and religious groups. With the exception of Africa, India harbors more genetic diversity than other comparable global regions. It is generally believed that the tribal people, who constitute 8.2% of the total population (2001 census of India), are the original inhabitants of India. The total number of tribal groups is estimated to be 461, who speak about 750 dialects that belong to one of the four language groups, Austro-Asiatic, Indo-Europeans, Dravidian and Tibeto-Burman . It is possible that populations living in close geographic proximity are more likely to exchange genes, thereby enhancing genetic similarity, despite the fact that these populations may not belong to the same socio-cultural stratum. Religious groups in India have some characteristic life style differences, which may influence the occurrence of cancer . During the 10-year period 2000 to 2010 the break-down by religion was as follows; 84.88% patients were Hindu, 13.31% were Muslim and 1.81% were Christian.

A large percentage of Indians, particularly Hindus, practice vegetarianism and avoid meat and fish products in their diet. Vegetarian diets have been associated with decreased risk for prostate cancer . Case-control studies that compared non-vegetarian and vegetarian diets and alcohol and tobacco use in India have reported that vegetarians have a reduced risk of oral , esophageal, and BCs . Vegetarian diets rely on pulses (e.g., beans, chickpeas, and lentils) as a source of protein, and pulses have been significantly associated with reductions in cancer . The present study comprised 61.30% patients following vegetarian diet while 38.70% eat non-vegetarian food. This may be because, most of the patients from Hindu community (84.88%).

Anthropometric factors of weight, height, and body mass index (BMI) have been associated with BC risk . Obesity leads to increased levels of fat tissue in the body that can store toxins and can serve as a continuous source of carcinogens . Body fat is an important locus of endogenous estrogen production and storage, and hence, could increase the risk of BC . There is considerable evidence that free estrogen levels are raised in obese women, especially in those with abdominal (visceral) obesity . Also, there is an increase in the bio-available estrogen fraction which may promote tumor growth, either directly or by modulating steroid activity and has been implicated as a risk factor for BC .

The incidence of breast carcinoma was more on the left side corroborating with the previous reports . The possible explanations are that the left breast is bulkier and the upper outer quadrant has a relatively larger volume of breast tissue .

Histologic types of BC in India are characterized by a high frequency of infiltrating duct carcinoma. Medullary, lobular, and squamous cell carcinoma were typical histological varieties of the older age groups, whereas ductal carcinoma was encountered mostly in premenopausal women . Our study as well as reports from India and the western world indicate that IDC is the most commonly encountered histopathology .

Family history of BC was present in 7.19% of the cases which is slightly lower than 10% seen in developed nations as well as that seen in Bahrain and Malaysia where family history was seen in 20% & 16.2% respectively but in Shanghai the same was 3.2% . A family history of BC in the mother, father, sister or daughter increases the risk of BC and the risk is even stronger if the family member was diagnosed before the age of 50 years old and/or with pre-menopausal BC . Specifically, if a woman has a first-degree relative >50 years diagnosed with post-menopausal BC, her risk increases by 80% whereas a first-degree relative with pre-menopausal BC increases a woman's risk by 330% . The risks increase for a higher number of first- and second-degree relatives diagnosed with BC . A history of ovarian cancer in other relatives (in the mother's or father's families) also increases the risk of BC . Hence family history in our population attains greater importance by virtue of the disease occurring in much younger age group .

In conclusion, this epidemiological study helps to know the incidence of BC in this region and to some extent the associated probable risk factors. Despite much research, BC persists as a major health burden. India has no available source of comprehensive epidemiological, clinicopathological, and outcomes data for BC patients . It is likely that the descriptive epidemiology of BC will continue to provide insights into the aetiology of the disease and will allude to the role of primary prevention, early diagnosis and treatment.

The mean age of presentation for breast carcinoma is a decade earlier in our patients compared to patients from the west. Hence, mammography as a screening tool is less likely to be as effective; due to higher density of breast tissue at younger age decreases the sensitivity of mammography and inability to afford mammography due to poor socioeconomic background.

An organized large-scale BC screening program does not exist in India. The few BC screening programs available are largely targeted at small communities, covering a miniscule proportion of the Indian population, and they rely on funds derived from research grants or the screened individuals' own resources. There is no government-funded or aided mass breast screening program available; experts also advocate screening based on periodic breast examination by a physician and breast self-examination . Population-based BC screening is not recommended in India due to limited resources and the lack of local statistics on mammography and BCs. The increasing burden of BC in Indian women warrants rigorous epidemiological investigations of trends observed in different rural, semi-urban and urban populations.

Nearly all Indian BCs are clinically detected; almost none are detected by screening . Hence considering the younger age of onset of BC and the rural background combined with poor socioeconomic status of majority patients there is a need for the evaluation of screening efficacy in Indian settings for determining the best screening strategy in different Indian sub-populations. Similarly the BC management strategies should to standardize to fit specific populations.

This is only a hospital records based study. However this study provide leads for further etiological research, identify the high risk groups that have greatest impact in BC development and helps to take-up BC preventive measures and screening programmes in early detection of BC.

Acknowledgments. Authors must declare all financial support for the research and any conflict of interest, including directorships, stock holdings, and contracts. The Journal of Epidemiology would not wish authors to be embarrassed if any undisclosed conflicts of interest were to emerge after publication. Aid with technical issues, statistical analyses, photography, or stenography and advice from colleagues can also be acknowledged.

Acknowledgment: