Reproductive risk factors and Breast cancer : a case control study from rural India

Background: Breast cancer is the most common type of cancer in women and is influenced by reproductive factors perceived by women worldwide. Aims: To identify the reproductive risk factors of breast cancer in newly diagnosed cases and to find out the strength of association of the risk factors with the breast cancer. Material and Methods: A hospital based case-control study was conducted in Satara district, India during year 2009 to 2011 among newly diagnosed cases of breast cancer and matched controls. A total of 434 participants including 217 cases and 217 controls were enrolled by purposive sampling technique from selected hospitals of study area. The information was collected by employing pre-tested questionnaire by utilizing interview method. Statistical Analysis used: Descriptive statistics, Odds ratio and Chi-square test was used to find out strength of association and statistical significant difference. Results: Highest proportion [31.80%] breast cancer cases was in age group 40-49 years with lowest age of 25 years at diagnosis of the disease. A very high proportion of both cases [88.02%] and controls [67.28%] were Hindu by religion and were from rural residence. Maximum proportion of breast cancer cases were housewives [63.59%], literate [71.42%] and from upper economic class [56.68%]. The proportions of cases were higher as compared to the controls with respect to risk factors like unmarried status, nulliparity, history of abortion, post menopausal status, absence of breast feeding and the history of exposure to hormonal contraceptives. The risk of getting breast cancer as indicated by Odds ratio was 8 times higher in unmarried women, 2.8 times in nulliparous women, 2.4 times with post menopausal status, 10.4 times with absence of breast feeding, 1.5 times with exposure to hormonal contraceptives and 4.5 times with history of ovarian disease respectively. Conclusion: The reproductive risk factors such as unmarried status of women, nulliparity, menopause, absence of breast feeding, history of ovarian disease and use of contraceptives were strongly associated with breast cancer.


Introduction:
Breast cancer is the most common type of cancer in women worldwide.It is reflected as an important public health problem for adult women residing in developing countries like India. 1 Breast cancer alone accounts for 16% of all female cancers 2,3 with 14% mortality, of which about half of the cases and 60% deaths are estimated to occur in economically developing countries. 4It is estimated that by 2030 the global burden of breast cancer will increase to over 2 million new cases per year. 5he age incidence rate of breast cancer in urban Indian women has been 25 to 30 per 100,000 women per year.The average increase in breast cancer cases over a period of last 30 year in Mumbai was 11% per decade.Breast cancer is increasing both in young under the age 40 yrs [11%/ decade] and old women above the age of 40 yrs [16 %/ decade].There are an estimated 100,000 to125, 000 new breast cancer cases detected in India every year and this number of breast cancer cases in India is estimated to double by 2025. 6he factors that contribute to the international variation in incidence rates of breast cancer largely stem from differences in reproductive and hormonal factors and the availability of early detection services.Reproductive factors which increase the risk of breast cancer include menopausal status of women, Bangladesh Journal of Medical Science Vol.14 (3)  nulli-parity, use of postmenopausal hormone therapy, oral contraceptives, failure of breast feeding, late age at first birth etc. 7 Epidemiological studies have shown that the incidence of breast cancer has increased in developing countries; however there is limited data about the reproductive risk factors related to breast cancer in these countries. 8atara is one of the district in the state of Maharashtra, India where 68% population resides in rural areas.Since last two to three decades, there is sociodemographic, economic and cultural transformation happens among women due to increase in educational level of women.This transformation has also brought about many lifestyle changes, such as increase in the habit of smoking, increase the marital age and first pregnancy, decrease the duration of breast feeding, decrease in fertility and changes in dietary habits.It is well known that breast cancer stood the rank second amongst the all cancerous conditions in Indian women. 8But till date no one has studied the problem to identifying reproductive risk factors of breast cancer faced by women residing in rural area of Satara district.
The aim of this study was to assess the strength of association between identified reproductive risk factors and breast cancer among the women residing in Satara district, western Maharashtra, India.The results of this study can contribute to the better understanding of specific reproductive risk factors for breast cancer which will be helpful to formulate a public health policy for increasing the awareness among women which will reduce the burden of the disease.

Materials and Methods:
The hospital based case-control study was conducted in Satara district of the state Maharashtra, India.standard deviation, and frequency percentages were calculated.Exposure rate of various risk factors in both cases and controls was found out for existence of association between the risk factors and the breast cancer.The strength of association was found out by using Odd's ratio at 95% confidence interval.
The association between the risk factor and the breast cancer was analyzed by using chi-square test.
Statistical significance was considered when p value was less than 0.05 at 95% confidence interval.

Results:
In all, 217 women with breast cancer and 217 from the control group were interviewed.The big gap in proportion of breast cancer cases with respect to religion could be due to the difference in the religion wise distributions in the populations groups in the India.Similar findings also have been reported by Badve RA (1990) 11 as 82.4%, 7.3% and 2.7% respectively for the Hindues, Muslims and Christiens and shows apparent difference when compared with our study and this difference could be due to time period of both the studies.The majority of breast cancer cases [63.89%] in our study are housewives and similar findings are also observed by Pakseresht S et al (2009). 9The proportion of illiterate to literate breast cancer cases are 28.57% and 71.43% respectively and this In our study, the rate of occurrence of breast cancer cases is higher among women from upper economic class.A study is conducted in rural area but modern agriculture, cash crop of sugar cane associated with higher economic status, increased literacy and sound economic status could be responsible for high incidence of breast cancer among upper economic class rural population.Similar findings have been observed by Kelsey JL(1979) 13 from developed country.The behavioral aspects of upper economic class may be related to occurrence of breast cancer like having less number of children, late marriage etc.In the present study, out of 217 breast cancer cases 3.68% women having breast cancer have not been married and risk of getting breast cancer has been 8 times higher in these women as compared to married ones.Similar findings have also been noted by Parameshwari P (2013) 12 and Pakseresht S et al (2009). 9The present study reveals, nearly 5.6% breast cancer cases are nulliparous and risk of getting breast cancer is 2 times higher in nulliparous women as compared to parous women.The parous women who have experience in pregnancy and breast feeding might have a protective effect on incidence of breast cancer.It could be due to the differentiation of mammary tissue during pregnancy 14 and a permanent reduction in prolactin production.Prolactin increases cell proliferation and decreases apoptosis in the breast.An increased risk of breast cancer in nulliparous women could be due to hormonal changes i.e. high levels of estrogen and progesterone.Similar findings are also noted by Mandana et al (2002) 15 and Rosner B(1994). 16mong breast cancer cases, the rate of abortion is 21.65% and indicates a risk for breast cancer with odd's ratio of 1.6 with confidence interval of 1 to 2.7.Similar finding has also been reported by Ozmen V (2009). 17However several other studies have contradictory results about association of abortion and breast cancer and actual patho-physiology has not yet been fully understood. 18e risk of developing of breast cancer is 2.5 times higher in women with menopausal status as compared to non menopausal status.The menopause increases the risk of breast cancer by maximizing cumulative ovarian hormone exposure which is responsible for initiation of cancer process. 14The risk of developing breast cancer is 10.5 times higher in women who have not made an attempt of breast feeding as compared to breast feeding women and it indicates the absence of breast feeding to be a risk factor for breast cancer.Similar findings also have been reported by Pakseresht S et al(2009) 9 and Parameshwari P(2013). 12Breast feeding is thought to reduce breast cancer risk by reducing the total number of ovulatory menstrual cycles and have effect on ovarian hormones. 19ur study shows the risk of getting breast cancer is 1.6 times higher in women with use of OC pills and DMPA as contraceptive hormones as compared to non users.Studies conducted by Ozmen V (2009) 17 , Lodha R (2011) 20 have also observed similar findings.Similar findings have also been reported by Ozmen V (2009). 17However a study conducted by Hulka BS (2001) 21 and Heiss G(2008) 22 have observed that hormone replacement is a risk factor for breast cancer and difference has been mainly due to use of estrogen alone or in combination with progesterone which enhances the breast cancer effect as compared to progesterone alone. 14The ethinyl estradiol and progestin and these hormones would provide higher levels of estrogen and progestin during an oral contraceptive cycle than normal ovulatory cycle and which might be responsible for breast cancer.The strength of association between history of ovarian disease or oophorectomy and breast cancer is 4.5 times higher in cases as compared to controls with significant statistical association [p < 0.05].A similar finding also has been reported by Adam (2001) as of odd's ratio of 1.48 with confidence interval of 0.79-2.54.23   Women with BRCA1 or BRCA2 gene mutations have a significantly increased risk of developing breast cancer and ovarian cancer.After oophorectomy women have been kept on hormone therapy which could further increase the risk of developing breast cancer as stated by Boyd S (1900). 24

Conclusion:
Our study revealed that, maximum breast cancer cases were in age group 40-49 yrs.The reproductive risk factors such as marital status of women, nulli-parity, post menopausal status, absence of breast feeding, history of ovarian disease and use of contraceptives were strongly associated with

Table 1 [A]: Demographic distribution of cases and controls demographic
, economic characteristics of the women, reproductive characteristics like age at menarche, number of children, menopausal status [artificial or physiological], hormonal contraceptive history and breast feeding etc. was utilized to collect the data from the cases and the controls through individual, personal interview method on schedule basis.The Patient's comfort was maintained and checklist was used to avoid duplication of cases and controls.The data so collected was entered into Microsoft Excel 2007 and analyzed by using Statistical Packages for Social Sciences [SPSS] statistical software version 17. Descriptive statistics i.e. mean,

Table 1 (B): Demographic and economic distribution of cases and controls
They were in the age group ranging from 25 to 70 years with the mean age of 48.59 and 48.43 years for the cases and the controls respectively.With respect to age, religion and residence, maximum 31.80 %, 88.02% and 67.28% of both cases and controls were in age group of 40-49 yrs, Hindu by religion and residing in rural area respectively.
[Table 1[B]].The proportion of ever married and unmarried women was higher in cases [86.18% and 3.69%] as compared to controls [83.87% and 0.46%] and the risk of getting breast cancer was 8 times higher in unmarried women as compared to the ever married women.The [* = p value < 0.05 at 95% confidence interval ] proportion of nulli-parous women was higher in the cases [5.07%] as compared to the controls [1.84%] and the risk of getting breast cancer in nulli-parous women was 2.8 times higher as compared to parous

Table 2 : Association of Reproductive risk factors with breast cancer
The majority of breast cancer cases, 67.28% have been from rural area as compared to the urban area.However study conducted byPakseresht  S et al(2009)from urban area of Delhi 9 have shown maximum breast cancer cases to be from urban area and difference could be related to the placement of hospital and the population catered by it.The present study is conducted in Satara district where approximately 80 % population is residing in the rural area and the district is known to be from sugar belt of western Maharashtra.In this study, majority of breast cancer cases, 88% are from Hindu religion and proportion of Muslim and Christians has been 8.7% and 3.2% respectively.