|BREAST CANCER SYMPOSIUM - ORIGINAL ARTICLE
|Year : 2014 | Volume
| Issue : 3 | Page : 251-255
Reproductive risk factors associated with breast carcinoma in a tertiary care hospital of north India: A case-control study
R Babita1, N Kumar1, RK Karwasra2, M Singh2, JS Malik1, A Kaur1
1 Department of Community Medicine, Pt. B.D. Sharma, PGIMS, Rohtak, Haryana, India
2 Department of General Surgery, Pt. B.D. Sharma, PGIMS, Rohtak, Haryana, India
|Date of Web Publication||10-Dec-2014|
Department of Community Medicine, Pt. B.D. Sharma, PGIMS, Rohtak, Haryana
Source of Support: None, Conflict of Interest: None
Context: Worldwide, breast cancer is the most common cancer among women. In India and other developing countries, breast carcinoma ranks second only to cervical carcinoma among women. But the incidence of breast cancer is on the rise and may become number one cancer in females in near future. Aims: (1) To find out the magnitude of reproductive risk factors of carcinoma breast among the study subjects; and (2) to find out the association of reproductive risk factors with breast carcinoma. Materials and Methods: The study was done in the wards of General Surgery and Oncosurgery from August 2009-July 2010 in a tertiary care institute. A total of 128 histopathologically confirmed cases of breast cancer those came in this duration were considered. Equal controls were selected by simple random sampling by lottery method. The controls were matched for age with a range of ± 2 years. The subjects were interviewed using a pre-tested questionnaire. Written informed consent was taken from study subjects before starting the interview. Statistical Analysis Used: Chi-square test, odds ratio with 95% confidence interval, and t test. Results: The age group of the cases was 25-78 years, whereas that of the controls was 24-79 years. The difference among cases and controls regarding age at marriage, age at menarche, age at menopause, age at first pregnancy, and number of children was statistically significant. Continuous variables of the study population were analyzed by independent t tests, in which age at menarche and age at first pregnancy were found statistically significant. Conclusions: Information, education, and communication activities regarding risk factors and breast self-examination should be imparted to the women to create awareness about this fatal disease.
Keywords: Breast cancer, case control, risk factors
|How to cite this article:|
Babita R, Kumar N, Karwasra R K, Singh M, Malik J S, Kaur A. Reproductive risk factors associated with breast carcinoma in a tertiary care hospital of north India: A case-control study. Indian J Cancer 2014;51:251-5
|How to cite this URL:|
Babita R, Kumar N, Karwasra R K, Singh M, Malik J S, Kaur A. Reproductive risk factors associated with breast carcinoma in a tertiary care hospital of north India: A case-control study. Indian J Cancer [serial online] 2014 [cited 2019 Aug 22];51:251-5. Available from: http://www.indianjcancer.com/text.asp?2014/51/3/251/146759
| » Introduction|| |
Worldwide, breast cancer is the most common cancer among women. Globally, every 3 min a woman is diagnosed with breast cancer, amounting to one million cases annually. According to World Cancer Report the incidence could go up to 1.5 million by 2020.  It is reported that 1 in 22 women in India is likely to suffer from breast cancer during her lifetime, while the figure is definitely more in America with 1 in 8 being a victim of this deadly cancer.  In India and other developing countries, breast carcinoma ranks second only to cervical carcinoma among women. But the incidence of breast cancer is on the rise and may become number one cancer in females in the near future. The age-adjusted incidence rates varied between 16 and 25/100,000 populations. At present, India reports around 100,000 new cases annually. According to a study by the International Agency for Research on Cancer (IARC), there will be approximately 250,000 new cases of breast cancer in India by 2015. 
Under the National Cancer Registry Programme (NCRP), the Indian Council of Medical Research commenced a network of cancer registries across the country in December 1981. The consolidated report of population-based cancer registries (PBCRs) was published in 2005. It consisted of 2 years data (1999-2000) of the 5 urban (Bangalore, Bhopal, Chennai, Delhi, and Mumbai) and 1 rural (Barshi) PBCR. The report released in December 2006 covers (a) the data of the 6 registries-Bangalore, Bhopal, Chennai, Delhi, Mumbai, and Barshi for the years 2001-2003, (b) the 6 PBCRs (Aizawl District, Dibrugarh District, Kamrup Urban District, Silchar Town, Imphal West District, and Sikkim State) in the North East for the year 2003-2004, and (c) that of the Ahmedabad PBCR covering Ahmedabad District (other than Ahmedabad Urban) for the year 2004. In the PBCR report, among females, breast cancer was the leading site of cancer in all registries, except in Barshi. This was followed by cancer cervix as the second leading site of cancer. In Barshi, the leading site of cancer was cervix uteri constituting 36.8% of all cancers followed by breast. Hospital- based cancer registries reported more cases of breast cancer than cervical cancer in Mumbai, Dibrugarh, and Thiruvananthapuram and more cases of cervical cancer than breast cancer in Bangalore and Chennai. The increase in the breast cancer cases is mainly being documented in the metropolitan cities; but this data is not totally reliable as many cases in the rural areas go unnoticed. 
Reproductive and hormonal factors contribute most to the development of breast cancer. Among these, the high-risk reproductive factors are Early menarche, late menopause, late first full-term pregnancy and nulliparity  Nulliparity, more age at first live birth and no breastfeeding are major reproductive risk factors for breast cancer in the developed countries. The role of reproductive factors in the development of breast cancer in Indian population is different as compared with that seen in the western population. This is because parity, younger age at first live birth, and lactation practices are part of our culture, whereas these factors are far less prevalent in western women.
Geographic variation in the incidence of breast cancer can be attributed to exposure to various risk factors. Risk of breast cancer increases in successive generations of people moving from low-risk areas to high-risk regions proving that changes in reproductive behavior and lifestyle are more important than hereditary factors in the development of breast cancer.  These factors are mainly responsible for the variation in breast cancer incidence seen in different regions of the world by virtue of their different prevalence in these regions.
The following study was undertaken to find the magnitude of reproductive risk factors and the association of these factors with carcinoma breast among the study subjects in a tertiary care hospital of north India.
| » Aims|| |
• To find out the magnitude of reproductive risk factors of carcinoma breast among study subjects.
• To find out the association of reproductive risk factors with breast carcinoma.
| » Materials and Methods|| |
An interview based case-control study was carried out in the wards of Oncosurgery and General Surgery in a tertiary care institute of north India. About 125-150 new patients of breast carcinoma are admitted annually for treatment in the Department of Oncosurgery in this institute. All the newly diagnosed women with breast cancer admitted in the Oncosurgery ward during 1-year period were taken as study subjects. The study was conducted from August 2009 to July 2010. A written informed consent was taken from study subjects before starting the interview.
A total of 128 women, with histopathologically confirmed breast cancer, who consented were included in the study The study subjects were interviewed once only and their registration number were recorded to prevent double counting of the same subject. Wards were visited twice weekly and any new cases were included in the study, after explaining the objectives of the study to the subject.
Controls were selected from the indoor female patients admitted for a wide spectrum of general surgical procedures in the General Surgery ward of the same institute without having any type of cancer. Controls were also selected twice a week by simple random sampling using lottery method. Controls were matched for age with range of ±2 years. Case to control ratio was 1:1. Study subjects were interviewed personally and the information was recorded in the semi-structured pretested proforma. Women were labeled as menopausal if they have not menstruated during the previous 6 months before the date of data collection.
The primary concern was on quality of data collection. An attempt to minimize recall bias, associated with timing of a particular event, was made by asking questions about the related important events in the respondent's life; for example, information about age of menarche was not remembered correctly by some of the respondents, in these respondents information was deduced by correlating age of menarche with the age of marriage.
Exclusion criteria for cases
- Women with hysterectomy and artificial menopause
- Women aged <20 years and >80 years.
Exclusion criteria for controls
- Women with hysterectomy and artificial menopause
- Women aged <20 years and >80 years
- Women with breast or any other carcinoma.
The categorical data were analyzed statistically using Chi-square test and odds ratio (OR) with 95% confidence interval (CI). Continuous variables were analyzed using independent t test. All the analyses were performed with Statistical Package for Social Sciences (SPSS) version 17.
| » Results|| |
All the data were coded and entered into computer. Cases and controls were matched for age with the range of ±2 years. Age group of the cases was 25-78 years, whereas that of the controls was 24-79 years. Maximum number of the cases (93.8%) and controls (97.7%) belonged to the Hindu community; rest of the study population comprised Muslims and Sikhs. No Christians could be included in the study. The proportion of cases (56.3%) and controls (63.3%) living in rural areas were more than those living in the urban areas.
In maximum cases (54.7%), the age at marriage was between 15 and 20 years, followed by <15 years age group, whereas in the control group, maximum subjects married before 15 years. Women who got married before 15 years of age have decreased risk (OR 0.466, 95% CI 0.274-0.793), whereas increased risk among those who got married after 20 years (OR 1.363, 95% CI 0.582-3.193), as compared with the women who got married between 15 and 20 years of age. The difference was found to be statistically significant (P value 0.005). The most common age at menarche among cases and controls was between 13 and 15 years. Women who had menarche at an early age (<13 years) were at increased risk (OR 3.726, 95% CI 1.830-7.588), whereas those having menarche after the age of 15 years were associated with decreased risk of developing breast cancer (OR 0.869, 95% CI 0.454-1.666), as compared with women who had menarche between 13-15 years of age. Age at menarche could not be determined in 6 cases and 8 controls. The difference found was statistically significant (P value 0.003). Approximately one third of the study subjects were premenopausal. Risk of carcinoma increased as the age at menopause increased. The risk of carcinoma was less among cases who had had menopause before 45 years of age, and the risk was more among cases who had had menopause after 50 years of age compared with 45-50 years age group. Age at menopause could not be determined in 2 cases and 3 controls. The difference found in age at menopause was statistically significant (P value 0.002) [Table 1].
|Table 1: Distribution of study population by age at marriage, age at menarche, and age at menopause|
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In majority of cases age at first pregnancy was between 20 and 25 years of age, while majority of controls had their first pregnancy before 20 years. The risk of breast carcinoma was less in females who had their first pregnancy before 20 years, and more in cases who conceived for the first time after 25 years, when compared with subjects of 20-25 years age group. The difference found in age at first pregnancy was statistically significant (P value < 0.0001). Out of 128 cases, 4 had no child, but all the controls had one or more children. The categories with ≤2 children and 3-4 children had 21.9% and 57.8% of the controls, respectively, and 34.4% cases each. The risk of developing breast carcinoma was more among the females with ≤2 children, as compared with females who had 3-4 children. A 3.1% cases were nulliparous, but none of the controls. The difference regarding the number of children was statistically significant (P value ≥ 0.001) [Table 2].
|Table 2: Distribution of study population by age at first pregnancy, number of children, and abortion|
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Continuous variables of the study population were analyzed by independent t tests. The mean age of cases was 49.98 ± 11.6 years and the mean age of controls was 49.54 ± 12.0; cases and controls were matched for the age at diagnosis with a range of 2 years. Cases and controls differed significantly by age at marriage and age at first child birth. Cases and controls did not differ significantly by age at menarche and age at menopause [Table 3].
More than half (56.3%) of the study subjects had breast carcinoma on left side, and 39.8% on right side. In 3.9% cases breast cancer was present on both sides.
| » Discussion|| |
The risk factors responsible for the causation of breast cancer may be population or region specific. There is international variation in the incidence of breast cancer, the reason for which is unclear. However, rates in low- risk population increase after migration to high-risk areas, and in subsequent generations approximate to those of the host population.
In the present study, the risk of breast carcinoma was more among cases who have had first pregnancy after 20 years as compared with cases who have had first pregnancy before 20 years of age. The difference found was statistically significant. Helmrich et al. also reported significant trend of increasing risk with increasing age at first birth, women who had first pregnancy after the age of 35 years had 40% increased risk compared with those with first pregnancy before the age of 20 years.  Findings of some other studies were similar to the present study. , This observation supports the hypothesis that, pregnancy at a younger age is associated with a favorable estrogen profile, which drastically reduces the presence of undifferentiated/vulnerable breast cells, differentiates terminal end buds to lobules, and/or reduces the pool of estrogen receptor-positive cells. In the present study, women who got married before 15 years of age have decreased risk compared with women who got married after 20 years of age. The difference was found to be statistically significant. A study done by Ebrahimi et al. found that never married women were at a higher risk for breast cancer.  Although marital status by itself is not a determining factor for increased or reduced breast cancer risk, but the main protective effect is from early first full-term pregnancy.
In our study, women who had menarche at an early age (<13 years) were at an increased risk compared with women who had menarche at 13-15 years of age. Menarche after the age of 15 years was associated with decreased risk of breast cancer and the difference was statistically significant (P value 0.003). The findings were similar to a study done by Ewertz et al., in which trends of decreasing risk were observed by increasing age at menarche and it was found statistically significant.  Similar observations were found by many other studies. ,,,, Gajalakshmi and Shanta found that study subjects did not differ regarding early menarche and Harrison et al. found menarche before 11 years of age as protective. , The effect of age at menarche on breast cancer risk may be mediated simply by the prolonged exposure of breast epithelium to estrogen produced by regular ovulatory cycle.  In addition, some studies have demonstrated that women with early menarche have higher estrogen levels than women with later menarche for several years after menarche.  Ghausia Masood et al. also found a history of early menarche (below 13 years of age) was observed to be protective for all women but the protection from early menarche was not observed to be statistically significant in the separate analysis of premenopausal and postmenopausal women in their study.  This sort of result for Asian studies may be due to the recall bias, especially among older women.
In the present study, risk of carcinoma increased as the age at menopause increased. The risk of carcinoma was more among cases who have had menopause after 45 years as compared with cases who have had menopause before 45 years. The difference found was statistically significant. Meshram et al. reported that menopause (≥50 years of age) was observed to be associated with increased risk and the risk was 7.9 times more among women who had menopause at or after 50 years of age as compared with women who had menopause before 45 years.  Similar findings were reported by many other studies. ,, The effect at age at menopause may be mediated by prolonged exposure of breast epithelium to estrogen. Helmrich et al. found that high parity was associated with a reduction in the risk for parity >5, compared with women with 1-2 parity.  Gomes et al. found significant difference in parity of less than 6 deliveries and nulliparous women.  Kato et al. found that females having fewer births were at increased risk of breast cancer, further lower parity and single marital status were stronger for premenopausal breast cancer.  Many other studies found similar findings. ,,, Findings of our study were similar to all the above studies. Indian women have more children than do western women, and this is one of the major causes of low incidence of breast cancer in Indian population as compared with western population.
| » Conclusion|| |
In the present study, history of late marriage and late age at first child birth are the significant risk factors for breast cancer, which are modifiable. Information, education, and communication activities regarding these risk factors, early signs and symptoms of breast carcinoma, and breast self-examination should be imparted to the women to create awareness about this fatal disease. A targeted intervention to tackle this problem seems to be the need of the hour.
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[Table 1], [Table 2], [Table 3]