EPIDEMIOLOGICAL STUDY ON THE RELATION BETWEEN BREAST CANCER RISK AND ENDOGENOUS HORMONAL STATUS OF WOMEN IN TRANSYLVANIA COUNTY

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1 EPIDEMIOLOGICAL STUDY ON THE RELATION BETWEEN BREAST CANCER RISK AND ENDOGENOUS HORMONAL STATUS OF WOMEN IN TRANSYLVANIA COUNTY BOGDANA NASUI, NINA CIUCIUC, DELIA HERGHEA¹, MONICA POPA Department of Communitary Medicine, Hygiene Discipline University of Medicine and Pharmacy, Iuliu Hatieganu Cluj Napoca ¹Department of Epidemiology, Oncologic Institute Ion Chiricuta Cluj-Napoca Cluj Napoca, Nasaud Street, Nr. 6/3, Code ROMANIA Abstract Higher levels of endogenous hormones have long been hypothesized to increase the breast cancer risk. In a casecontrol study we assessed the reproductive factors linked to breast cancer risk (age at menarche, age at menopause, breast feeding, number of full-term pregnancies, age at first full-term ) using a validated questionnaire applied by interview to 223 breast cancer women and 211 controls. We calculated odds ratio to establish the relation between breast cancer risk and hormonal factors. The trend analyses shows the increasing or decreasing risk depending on the studied reproductive factors. The data were analyzed in Microsoft Excel 2000 and Epiinfo version The results were considered significant statistically in wich p<0.05. The results of the study shows that early age at menarche and late menopause was a risk for breast cancer females, whereas breastfeeding and higher parity protect against breast cancer. This results are important for hormonedependent cases of breast cancer that can be prevented by modifiable lifestyle and environmental factors. Key-Words: cancer risk, age at menarche, age at menopause, parity, breastfeeding. 1.Introduction Breast cancer is the most common cancer in women worldwide. Around 1.15 million cases were recorded in 2002, accounting for around 23 per cent of all cancers in women (11 per cent overall). Observed rates of this cancer increase with industrialization and urbanization, and also with facilities of early detection. It remains much more common in high income countries but is now increasing rapidly in middle- and low- income countries, including within Africa, much of Asia and Latin America. Breast cancer is the leading cause of death from cancer in women (fifth overall), accounting for 14 per cent of all cancer deaths worldwide [1]. Reproductive events are related to breast cancer. Risk is increased by an early onset of menarche, nulliparity, late age at first birth and late natural menopause. Breast feeding children reduces women s risk of developing breast cancer. A reduced number involves neoplasm family history wich is an important risk prediction, but in the most neoplasms etiology is not known. Certain risks determinants are related to the diet and their maximum effect is considered to appear early in lifetime (since puberty). A healthy lifestyle, including maintaining a normal body weight, regular physical activity and no alcoholic drinks can prevent 10-20% case of the breast cancer cases [2,3]. The objective of this study was to investigate the reproductive factors in relationship with breast cancer risk. This study is part of a greater research that establish the influence of life style factors in relation with breast cancer risk [4]. ISBN:

2 2. Materials and methods In order to achieve this aim we performed a case-control study which was applied on two populational groups: 223 cases, breast cancer patients hospitalized in the Oncological Institute Ion Chiricuta, Cluj-Napoca (Romania) and 211 controls, apparently healthy women, having the same social and economical status and living in the same geographical area. The average age of the lot under study was ± 9.40 for breast cancer patients and 55.3 ± for the controls ( p>0.05). Out of these, 39 were premenopausal women and 184 were postmenopausal women in comparison with 45 controls in premenopause and 166 controls in postmenopause. To investigate the hormonal status of both cases and controls we applied a valid questionnaire. The data were compaired with them from the hospital patients recordings. We assessed the age of menarche, age of menopause, number of full-term pregnancies, the age of first full term and breastfeeding in relation with breast cancer risk. The final results were expressed under the form of arithmetical mean. In order to compare the recorded average values we used the ANOVA statistical test. The probability of breast cancer emergence was estimated by calculating odds ratio depending on the variables that we investigated (age of menarche, age of menopause, etc). We used the liniar trend to estimate the tendency of breast cancer risk (i.e. the increasing or decreasing) depending on the menopause age. In this case we used chi square test to establish the statistical significance of the results [5,6]. The statistical data proccessing was done in Microsoft Excel 2000 and Epiinfo version programmes. Only the results whose value was p<0.05 were considered statistical significant. 3. Results Out of the results obtained we mention the most important ones. It was investigated the age of menarche onset to the breast cancer patients and controls. The average age of menarche was ± 1.80 years for breast cancer patients and ± 1.54 years for controls, p= with a statistical significant difference. We calculated odd ratio by dividing the populational groups in two subgroups: one females with the onset of menarche under 12 years and the other with the menarche over 12 years [tabel1]. The results of the study shows that early menarche (under 12 years) was a risk for breast cancer patients (OR= 3.62 p< 0.001) and the age of menarch after 12 was protective for this patients. On the other hand there were more breast cancer females (21.84%) than controls (7.17%) with earlier onset of menarche. Tabel 1 Breast cancer risk and the age at menarche Age at menarche OR CI 95% p <12 years 3,62 0,14-0,53 < 0,001 >12 years Age at menopause is another reproductive factor associated with breast cancer risk. The average age of menopause was ± 5.74 years for breast cancer patients and ± 5.54 years for controls, with a statistical significance p= We calculated odds ratio depending on the menopause age by dividing the populational group in tree subgroups of women: one with the age of menopause below 45 years, with the age of menopause between 45 and 50 years and a subgroup of women with above 50 years age of menopause. The results of the study shows that the age of menopause above 45 years was a risk for the breast cancer females (OR= 1.8, p= 0.017) [table 2.] Table 2 Breast cancer risk and age at menopause Age at menopaus e OR CI 95% p < 45 years 0,43 0,94-2,99 0, ,28 1,9-6,95 < 0,001 P for trend 0,0006, chi 2 = 27,21 years 1,8 1,1-2,93 0,017 > 50 years 1,67 0,27-0,68 0,0002 ISBN:

3 The linear trend of breast cancer risk depending of increasing age of menopause shows the increasing risk when the age of menopause increases (chi square=14.73, p= ) [fig. 1] breast cancer risk 2,5 2 1,5 1 0,5 0 chi square =14,73 P=0,0006 y = 0,685x - 0,07 R 2 = 0, age at menopause Fig.1 The trend analyses of breast cancer risk and the age at menopause The study estimated the relation between breast cancer risk with the numbers of completed pregnancies. The linear trend of breast cancer risk shows that the risk of cancer decreases with the increasing number of full-term pregnancies (p for trend 0.04) [fig.2]. breast cancer risk 2 1,5 1 y = -0,062x + 1,286 0,5 R 2 = 0,0421 chi square=6,93 P=0, number of full-term pregnancies Fig.2 The trend analyses of breast cancer risk and the number of pregnancies To assess breast feeding in relationship with breast cancer risk we divided the populational groups in three subgroups: women that have under 12 weeks of lactation, women with weeks of breastfeeding and females with more than 24 weeks of lactation. Duration of breast feeding was positive associated with a protective effect against cancer risk when it was more than 6 months (24 weeks) [table 3]. Table 3 Breast cancer risk and duration of breastfeeding Duration of lactation at first full-term OR CI 95% p < 12 weeks 1,25 0,64-2,44 0, weeks 2,49 1,42-4,37 < 0,001 > 24 weeks 0,44 0,27-0,72 < 0,001 In this study the age at first full-term below 30 years was a protective factor against mammary carcinogenesis, but not statistically significant [table 4] and the age at first above 30 years was a risk factor for breast cancer. Table 4 Breast cancer risk and age at first full-term Age at first full-term OR CI 95% p < 30 ani 0,77 0,23-2,5 0,84 > 30 ani 1,3 0,4-4,31 0,84 4. Discussion The average age at menarche has been declining world-wide for the last 200 years, at years in developed countries, thus the increase in breast cancer rates that have generally occured with industrialization correlate with decreasing average age at menarche. Early age at menarche is in part determined by rapid growth and development in females, within a range of genetic potential. Rapid growth and development are evidenced by greater height, in both childhood and adulthood. Great energy intake and energy-dense constituents (like saturated lipids, animal proteins and refined carbohydrates) and low levels of physical activities ISBN:

4 would lead to rapid growth and overweight or excess body fatness that can affect the age of onset of menarche. Previous studies conducted on the same populational group shows that obesity was a risk factor for the patients with breast cancer [7]. The biological pathway through wich earlier age at menarche leads to increased risk of breast cancer probably involves earlier and longer exposure over a lifetime to the hormonal milieu that accompanies regular menstrual cycles. In addition some studies have suggested that women who experience menarche at an earlier age have higher estrogen levels for several years after menarche and probably throughout their reproductive lives [8]. The results of the study shows that patients with breast cancer had an earlier age at menarche than the controls. It is possible that this patients had higher levels on endogenous hormones than the control females. Late menopause increases breast cancer risk due to the same biological pathway that involves higher levels of circulating estrogens [9]. The studies shows that menopause after 50 years was a risk factor for breast cancer patients and the risk increases with the increasing age of menopause, as the trend analyses shows (P for trend ). The practice of lactation has also been linked to lower risk for breast cancer through the delay in the reestablishment of ovulation following a completed [10]. This study shows a protective effect of breastfeeding when the duration is above 24 weeks (OR= 044, p < 0.001). Parity reduces the risk of breast cancer and the higher number of full-terms pregnancies, the greater the protection. The results of our study shows that increasing number of full-term pregnancies lowers the breast cancer risk (p for trend 0.04). This is thought to be related to lowered prolactin levels in parous compared with nulliparous women and higher levels of sex hormone binding globulin and lower levels of free estradiol than in nulliparous women [11]. The study shows no statistical significant results between the age at first full term above 30 years and risk of breast cancer (p= 0.84). The results of the study must be interpreted in close conection with the other major determinants of this pathology (genetic,) wich are unmodifiable factors. A substantial proportion of the breast cancer cases experienced in developed countries can be explained by factors wich influence exposure to estrogens, including reproductive and hormonal factors, obesity, alcohol and physical activity. Previous study conducted on the same populational group shows that alcohol consumption was a risk for breast cancer females [12]. Some hormones related factors can be influenced by a healthy lifestyle with a good nutrition (beginning in early life), being physically active and no/less alcohol consumption. It was estimated that around 30% of female breast cancers are linked to largely modifiable lifestyle and environmental factors [13]. 5. Conclusion The study reveals the importance of reproductive factors in breast cancer risk. Our results suggest that the early age at menarche (below 12 years), late age at menopause (above 50 years) were risk factors for breast cancer females, whereas breast feeding and parity were protective factors against mammary carcinogenesis. References [1] *** Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. World Cancer Research Fund & American Institute of Cancer Research, Washington DC, [2] ***World Cancer Research Fund & American Institute of Cancer Research: Food, Nutrition and Prevention of Cancer: a global perspective. Washington DC, 1997 [3] Pence, B. & Dunn M.D.,. Nutrition& Women's Cancers. Washington DC, CRC press [4] Nasui, B. 'Specific features of dietary pattern in relation with (mammary) carcinogenesis'. Ph.D. diss., University of Medicine and Pharmacy Cluj-Napoca, [5] Pangano M, Gavreau K: Principles of Biostatistics. 2 nd edition, Pacific Grove, CA: Duxbury Press; [6] Mitchell H. Katz, Study Design and Statistical Analysis, Cambridge University Press, New York, [7] Bogdana Năsui, Daniela Curşeu, Nina Ciuciuc, Monica Popa, Carmen IonuŃ. Study concerned the relationship between the ponderal status as a risk factor for the postmenopausal breast cancer, Clujul Medical, Vol. LXXX nr.4, 2007, ISBN:

5 [8] Huiyan Ma, Leslie Bernstein, Ronald K Ross, Giske Ursin, Hormone-related risk factors for breast cancer in women under age 50 years by estrogen and progesterone receptor status: results from a casecontrol and a case-case comparison, Breast Cancer research, 8: R39, [9] Bernstein L, Ross R K: Endogenous hormones and breast cancer risk. Epidemiol Rev,15: 48-65,1993. PubMed Abstract [10] 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 women with breast cancer and women without disease. Lancet, 360; 9328; , [11] Althuis MD, Fergenbaum JH, Garcia Closa M, Brinton LA et al.. Etiology of hormone receptordefined breast cancer: a systematic review of literature. Cancer Epidemiol Biomarkers Prev, 13: , 2004 [12] Bogdana Nasui, Monica Popa, Daniela Curseu, Dana Sirbu: Alcohol intake in relationship with breast cancer.. Revista Medico-Chirurgicală a SocietăŃii de Medici şi Naturalişti din Iaşi,, 113(3): , 2009 [13] Parkin DM, Boyd L, Walker LC : The fraction of cancer attributable to lifestyle and environmental factors in the UK in Summary and conclusions. Br J Cancer, 105 (S2): S77-S81, ISBN: