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ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 1  |  Page : 302-308

Relevance of risk factors of breast cancer in women: An Eastern Indian scenario


1 Department of Radiotherapy, Nil Ratan Sircar Medical College, Kolkata, West Bengal, India
2 Department of Community Medicine, Nil Ratan Sircar Medical College, Kolkata, West Bengal, India
3 Department of Radio-diagnosis, Lokmanya Tilak Municipal Medical College, Mumbai, Maharashtra, India
4 Research Unit, Jamini Bhushan Roy State Ayurvedic Medical College, Kolkata, West Bengal, India
5 Department of Radiotherapy, Radha Gobinda Kar Medical College, Kolkata, West Bengal, India

Date of Web Publication13-Apr-2016

Correspondence Address:
Ranen Kanti Aich
Departments of Radiotherapy, Simultala, Agarpara, North 24 Parganas, Kolkata - 700 109, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.160929

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 > Abstract 


Aims and Objective: Incidence of breast cancer is on the rise in developed as well as in developing countries. In India it has superseded cervical cancer as the commonest malignancy in women in urban areas. A lot of risk factors have been proposed from time to time that play a causative role in the natural course of this disease. However, they are based on data accumulated from studies conducted mostly in developed countries. Aim of this study was to find out whether these known and/or presumptive breast cancer risk factors hold true for women of developing countries like India also.
Materials and Methods: From 2008 to 2012; 1,463 breast cancer patients were compared side by side with 1,440 matched controls by predetermined questionnaire and anthropometric variables. Data were analyzed by Statistical Package for Social Sciences (SPSS) V19 software todetermine whether selected risk factors were more common in the patient group than the control group.
Results and Analysis: The risk factors under study were also found to be statistically significant for the study populationexcept duration of breastfeeding and family history of breast and ovarian cancers.
Conclusion: Risk factors for breast cancer do not differ significantly between developed and developing countries. Hence appropriate time has come for developing countries to incorporate breast cancer risk factors in health education and to consider pharmacological interventions in high risk women.

Keywords: Breast cancer, case-control study, developing countries, risk factors


How to cite this article:
Aich RK, Mondal NK, Chhatui B, Sepai HM, Aich R, Acharyya A, Manir K, Bhattacharaya J. Relevance of risk factors of breast cancer in women: An Eastern Indian scenario. J Can Res Ther 2016;12:302-8

How to cite this URL:
Aich RK, Mondal NK, Chhatui B, Sepai HM, Aich R, Acharyya A, Manir K, Bhattacharaya J. Relevance of risk factors of breast cancer in women: An Eastern Indian scenario. J Can Res Ther [serial online] 2016 [cited 2021 Jan 21];12:302-8. Available from: https://www.cancerjournal.net/text.asp?2016/12/1/302/160929




 > Introduction Top


The incidence of breast cancer has increased globally over the last decades.[1] Although traditionally less common, the greatest increase has occurred in Asian countries.[2] Various risk factors, for example, increasing age, early menarche, late menopause, nulliparity or first child birth after the age of 30 years, lack of breastfeeding, sedentary lifestyle, mutation of BRCA gene, etc., have been proposed. While some women having multiple risk factors never develop breast cancer, others may suffer from this disease in spite of not having a single risk factor. However, it may be assumed that women, who developed breast cancer, were more likely to have one or more of these risk factors than women who are free from this disease. Most of the data upon which risk assessments had been based are derived from studies done in western population.[3],[4],[5] Some of these risk factors had been confirmed by studies done on Chinese, Japanese, and Korean women.[6],[7] Data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program [8] indicated that the age-adjusted breast cancer incidence rates for women of racial/ethnic minority groups are substantially lower than those for white women. But in one multiethnic cohort, consideration of seven risk factors (ages at menarche and first birth, parity, age and type of menopause, weight, menopausal hormone therapy, and alcohol use) resulted in similar breast cancer risk in postmenopausal white, Hispanic, and African American women.[9] As incidence of breast cancer is gradually increasing in India as well, it has become very important to assess the risk factors in Indian women, to ensure health awareness, and to assess the cost/benefit of selected preventive measures.

Aim of this case–control study was to assess the increased prevalence of risk factor (s) in diagnosed breast cancer patients in comparison with an ethnically matched control population.


 > Materials and Methods Top


Our study group consisted of women with histopathologically proven breast cancer (of any age) attending a tertiary care center in eastern India between 2008 and 2012. The control population consisted of healthy women accompanying the above described patients, who were from the same locality but were not her first/second degree relatives. It was done to ensure the same socioeconomic, environmental, racial, and ethnicity match among 'study' and 'control' groups, while eliminating the familial trait of breast cancer. Permission was obtained from the institutional ethics committee (No: NMC/Ethi/Gen-25/3913). After obtaining proper informed consent, data on risk factors were collected by direct verbal and written questionnaire and anthropometric measurements were recorded. The data were analyzed using Statistical Package for Social Sciences (SPSS) software V19. The chance of BRCA negativity, risk of developing breast cancer in next 10 years as well as lifetime risk were calculated using IBIS model [10] and obesity was assessed by Mcleod Asian Scale;[11] both of which seemed to be more appropriate to our population. It is true that proper assessment of some of the risk factors like breast biopsy/cytology, mammography, germline mutation, etc., could not be done due to infrastructural limitations. But at the same time they can neither be incorporated in the mass awareness nor be used in mass screening programs.


 > Results and Analysis Top


In our study, a total of 1,463 women with diagnosed breast cancer (study population) were compared with 1,440 healthy women accompanying them (control population). Sociodemographic profile of the study and control groups has been shown in [Table 1].
Table 1: Socio-demographic profile of the study and control groups

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Age distribution

Mean ± standard deviation (SD) and median age of the two groups were comparable. On independent t-test, no significant difference was observed between two groups (P = 0.068). On Chi-square test, age group-wise distribution in the two groups was found to be significantly different (P < 0.05). Chances of developing breast cancer were found to be more in elderly age group when compared with less than 30 years of age; the most common age group being 'perimenopausal' (41–50 years). Odds of getting breast cancer in the age group of 41–60 years varied 1.31–1.65 times more compared to those of less than 30 years of age. Differences were found to be statistically significant [Table 1].

Educational status

Educational status is an indirect reflection of socioeconomic background. Comparative analysis of educational status, showed that maximum number of participants' educational level were below fourth grade. The distribution was not significantly different among the two groups (P = 0.397). The level of education also had no association with occurrence of breast cancer (odds ratio <1).

Menstrual status

In study arm, 56.3% (n = 824) of the women were premenopausal and 43.7% (n = 639) were postmenopausal; while in the control arm, 50.1% (n = 722) were premenopausal and 49.8% (n = 718) were postmenopausal [Table 2]. Distributions were significantly different in both the groups (Pearson Chi-square value = 11.7, P < 0.05). Odds of developing breast cancer in premenopausal women was higher than postmenopausal women in study arm (odds ratio = 1.2, P < 0.05).
Table 2: Distribution of study and control groups according to Reproductive factors

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Age at menarche

There was no significant difference in distribution pattern according to 'age at menarche' among study and control groups. The mean age ± SD being 13.4 ± 1.46 and 13.47 ± 1.6 years, respectively in the study and control groups [Table 4]. On independent samples t-test, differences were not statistically significant. But in multivariate analysis, chance of getting breast cancer was more among those with early age menarche [Table 2].

Age at menopause

Mean age ± SD of menopause in study and control arms were 44.2 ± 4.6 and 44.4 ± 5.6 years, respectively. On independent samples t-test, variances were not statistically different (P = 0.647) as shown in [Table 2]. On Chi-square test, distribution among two groups differed significantly (P < 0.05, Pearson's Chi-square value = 17) [Table 4]. On multivariate analysis, patients having late menopause (> 50 years) had more chance of having breast cancer than earlier ones (odds ratio = 1.7, Z = 3.73, P < 0.05).{Table 2}

Age at first full-term pregnancy

Median age of the study and control groups at the time of first full-term pregnancy were 20 and 18 years; mean ages being 21.4 ± 5 and 19.1 ± 3.7 years, respectively [Table 2]. On independent samples t-test, these differences were statistically significant (P < 0.05). In this study, 8.2% (n = 109) women with breast cancer had their first pregnancy after 30 years of age; which was significantly higher than women who had no breast cancer 0.9% (n = 12). Chance of having breast cancer was 10.5 times higher in elderly primigravida (odds ratio = 10.5, Z = 7.04, P < 0.001).

Parity

Median parity was 2 (range = 11) and 3 (range = 12) in study and control arms, respectively. Odds of having breast cancer after at least one full-term pregnancy was less (odds ratio=0.973, P < 0.005). The number of nulliparous women was significantly higher (n = 139; 9.5%) in the study arm than the control arm (n = 100; 6.9%). On analysis of all pregnancies, considering full-term as well as non-full-term; it was found that chances having breast cancer was more among nulliparous women (odds ratio = 1.4, Z = 2.6, P = 0.017).

Breast feeding

88.1% (n = 1289) women in the study population had history of breast feeding, which is significantly lower compared to control population (90.6%; n = 1,305) [Table 2]. Chances of having breast cancer was higher among women who had not breastfed their children (odds ratio = 1.4, Z = 2.2, P = 0.023).

Duration of lactation


Mean ± SD duration of lactation in study and control arms were 27.2 ± 19.5 and 25.7 ± 18 months, respectively; while median (range) values were 24 (144) and 24 (196), respectively [Table 2]. Average duration of lactation was significantly higher in study population (P = 0.038).

Family history of breast and ovarian cancer

In the study arm, 2.1% (n = 31) had a family history of breast cancer; whereas in the control arm, the incidence was 2.3% (n = 33). There was no statistically significant difference between the two arms [Table 3].0.8% (n = 12) women in the studyarm and 2.1% (n = 30) in the control arm had family history of ovarian cancer [Table 3]. On analysis, it appeared that chances of occurrence of breast cancer was less in women with family history of ovarian cancer as compared to those who did not have such a history (odds ratio 0.389, P < 0.05).
Table 3: Distribution of risk factors according to family history, BMI and BRCA mutation probability

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Table 4: Multivariate analysis of the risk factors variables in the equation

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Body mass index (BMI)

Mean BMI of the study and control arms were 23.6 ± 4.6 and 23.7 ± 4.7 kg/m 2, respectively. On independent samples t-test, variances were not statistically different among the two groups [Table 3]. Odds of occurrence of breast cancer were higher in normal weight (odds ratio 1.3 and P = 0.023) and overweight women (odds ratio 1.4 and P = 0.03) than underweight ones in the study arm. But this association was not statistically evident in obese group (BMI > 30kg/m 2) separately, while comparing two arms.

Laterality

Side-wise distribution of breast cancer was not influenced by any risk factor and occurred in almost equal frequency on either side (left: 49.52%, right: 49.41%, and bilateral: 1.17%).


 > Discussion Top


A 'risk factor' is any cause that affects a person's chance of developing a disease, including cancer. Presence of one or more risk factors of cancer does not mean that the person will develop the disease; whereas, absence of all risk factors does not guarantee a protection. However, it may be assumed that women who have already developed breast cancer have more chance of having one or more risk factor (s) than women who do not have this disease.

The greatest risk factor for developing breast cancer is aging, but the rate of increase is not linear. The risk doubles every 10 years until menopause, when the rate of increase slows dramatically. SEER incidence data [12] showed that from 2006 to 2010, the median age at diagnosis for breast cancer was 61 years in USA. X Close Table I-12 (http://seer.cancer.gov/csr/1975_2010/results_single/sect_01_table. 12_2pgs.pdf). But the median age is 10–15 years earlier in other parts of the world where life expectancy is shorter. The peak incidence rates of breast cancer in East Asian women occurs typically 1 or 2 decades earlier compared to their Western counterparts.[13] In Asia, breast cancer incidence peaks among women in their 40s.[14] Mean age of our breast cancer patients was 45 years; which is 16 years earlier than women of USA, but as per with other Asian women.

Breast cancer occurs more frequently in women of higher socioeconomic class and educational status. This is probably related to lifestyle factors.[3] We have used formal education as an indirect evidence of socioeconomic background as actual economic status cannot be obtained from our patients. In this study, formal education has not been found to have any significant impact on breast cancer occurrence.

A strong correlation between female sex hormones and development of breast cancer has been suggested by numerous studies. Girls who have their menarche before the age of 12 years have twice the incidence of breast cancer than those who undergo menarche after the same age.[4] Data from Breast Cancer Detection Demonstration Project [5] indicated that women who began their menstruation before the age of 12 years had a relative risk for breast cancer of 1.3 compared to those who began after the age of 15. The age of menarche is commonly earlier in western populations relative to east Asians.[6] The mean age of menarche was 13.5 years in both our study and control populations. Only 8% of our populations attained their menarche <11 years, whereas 88% attained after the age of 12 years. There was no significant difference between the study and control populations in this respect [Table 4]. But in multivariate analysis, lower age at menarche has been found to have significant effect on occurrence of breast cancer.{Table 4}

Women who did not attain menopause until the age of 55 years showed a relative risk of 1.22 compared to those who attained their menopause before the age of 45 years.[7] In comparison with women whose menopause occurred between the ages of 45 and 54 (relative risk 1), women with menopause before the age of 45 have a relative risk of 0.73 and women with menopause after the age of 55 have a relative risk of 1.48.[15] Trichopoulos et al., opined that for each year in age at menopause, the risk of breast cancer increases by approximately 3%.[16] There is considerable interethnic difference in the timing of natural menopause. White women living in USA have been reported to have an average age of menopause of <50 years.[17] Mean age of menopause was 44 years in our study as well as control groups. But in multivariate analysis, significantly higher number women of the study group had their menopause after the age of 55 years. Contrary to the reported literature, most of our breast cancer patients were premenopausal rather than postmenopausal.

Nulliparity or having first child after the age of 30 years, has a slightly higher risk of breast cancer development.[18] The highest risk group is those who have their first child after the age of 35 years. In this group, the risk appears to be higher than nulliparous women. The Brinton studies [5] reported that compared to a woman with a first live birth at an age <20 years, the relative risk for the nulliparous women was 1.67 and the risk for the woman having first child birth after the age of 30 years was 2.23. The protection conferred by an early pregnancy prevailed for pregnancies that ended in a live or stillbirth, but not for those that terminated earlier. A large study comprising 55,537 women, reported that nulliparity, low parity, and late age at first pregnancy were all associated with increased risk in Japanese women.[19] A recent meta-analysis showed that each child birth decreases the relative risk of breast cancer by 7%.[18] These led to the speculation that the initial mutagenic event occurs before the age of 18, probably during the period of rapid growth of breast during puberty and that the hormonal milieu of pregnancy at that time diminishes the oncogenicity of the mutated cells. On the other hand, the possible mechanism for the apparent increase in risk of women who have their first pregnancy after the age of 30 years might be due to the stimulatory effect of the altered hormonal environment of pregnancy. Early motherhood is a common practice among Indian women and most of our women of both the groups had their first full-term pregnancy between 18 and 29 years, with an average age of 21.47 and 19.08 years for the study and control population, respectively (P < 0.05). The women in the study group were also significantly at risk in terms of their first full-term pregnancy after 30 years compared to the control group. In this study, nulliparity was more common in the study group, whereas grand multiparity in the control group (P < 0.05).

Breastfeeding usually for a long duration is a common phenomenon among Indian women. With increasing urbanization, the prevalence of breastfeeding is gradually decreasing. Breastfeeding may slightly lower the risk of breast cancer, especially if continued for 1.5–2 years; probably by reducing a woman's total number of lifetime menstrual cycles. A large study reported that the relative risk of breast cancer decreases by 4.3% for every year of breastfeeding in addition to a decrease of 7% for each child birth.[18] In a multicentric, case–control study on breastfeeding and breast cancer risk in India revealed that lifetime duration of breastfeeding was inversely associated with breast cancer risk among premenopausal women, but no such protective effect was demonstrated in the postmenopausal women.[20] Breast feeding was done in a significantly higher number of women of the control group than the study group (90.4 vs 88%). Paradoxically, average duration of breastfeeding was significantly higher in the study group (27.2 vs 25.7 months) [Table 3]. Number of children and percentage of women who had breastfed their children confirmed the established risk factors, but duration of breast feeding did not.

Risk of developing breast cancer has been reported to be higher among women whose relatives have this disease. A total of 11–30% of women suffering from breast cancer have one or more first degree relatives with breast cancer, while up to 40% reported to have one relative of any kind with this disease.[21] The relative risk decreases with advancing maternal age at the time of diagnosis from 2.1 for women whose mother was diagnosed before the age of 40 years to 1.5 for maternal diagnosis after the age of 70 years.[22] Women with greatest risk of breast cancer include those with multiple first degree relatives having breast cancer, first degree relatives with young age at onset, or bilateral breast cancer.[23] History of breast cancer in first degree relatives was not a significant factor in our study population, but family history of ovarian cancer was significantly higher in control group which differs from other reported studies.

Obesity has been found to increase the breast cancer risk in postmenopausal women.[24] Analysis of pooled studies demonstrated the risk of breast cancer to be 30% higher in postmenopausal women with a BMI over 31 kg/m2 compared to women with BMI of 20 kg/m2.[25] The prevalence of obesity is far greater in western women than in east Asian women [26] consistent with the greater incidence of postmenopausal breast cancer in the west. In premenopausal women, an inverse relationship exists between BMI and breast cancer risk which is thought to be due to the greater number of irregular menstrual cycles, with decreased exposure to ovarian hormones, as seen in heavier women.[27] In our study, normal and overweight women had a higher chance of developing breast cancer than underweight women, but obese women did not possess a higher risk.

Mutation of BRCA gene can predispose a woman to hereditary breast and ovarian cancer. Initial studies indicated that the risk for carriers of BRCA mutations is very high, with an expected lifetime incidence approaching 90% by the age of 70 years.[28] But Begg [29] reassessed the risk associated with BRCA gene mutation and suggested that earlier estimates may have been too high. 'Twin' studies also have shown that genetic factors accounted for only 27% of breast cancer risk.[30] The idea that the impact of the mutated BRCA gene may be considerably less than previously believed is an important one, as tests are now available which can identify women who have defective BRCA genes and offer the choice to undergo prophylactic mastectomy to reduce the risk. In our study, chance of BRCA negativity was similar in both the groups, but risk of developing breast cancer in next 10 years as well as lifetime risk was statistically significant in study group as compared to control group [Table 2].

Relationship between use of oral contraceptive and breast cancer is controversial. Collaborative Group on Hormonal Factors in Breast Cancer [31] indicated that current or recent users of oral contraceptives have a small increase in the risk of breast cancer (relative risk (RR) =1.24). But other studies have not demonstrated the increased risk, even with long-term exposure (> years).[32],[33] Oral contraceptive use was not prevalent in either study or control groups of our population and none had used it for long-term.

As indicated by the Women's Health Initiative trial [34] and by the Million Women Study trial,[35] hormone replacement therapy in postmenopausal women using combined estrogen and progesterone increases the risk of breast cancer, but not with 'estrogen only' therapy. Postmenopausal hormone replacement therapy was practically unknown to both our populations.


 > Conclusion Top


From the present study, it may be concluded that risk factors for breast cancer in our population do not differ significantly from the established ones except duration of breast feeding and family history of breast and ovarian cancer. In our country, most of the patients come at an advanced stage reflecting low health consciousness, deficient infrastructure facility, and/or aggressive nature of the disease. Therefore, detection of proper risk factors and their relative influence is of paramount importance as their incorporation in health education and pharmacological interventions in high risk women may reduce the incidence of this malignancy.

 
 > References Top

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