We are aware that this hospital based study has some potential biases such as selection biases (non response bias, hospital admission bias, exclusion bias), and information bias (interview bias, recall bias, reporting bias). One form of hospital admission bias, the problem is that hospitalized individuals are more likely to suffer from many illnesses or symptoms. Thus they are probably not representative of the target population. On the other hand, Istanbul University Istanbul Medical Faculty Hospital is one of the busiest hospitals located in Istanbul and over 80% of the outpatients reside in the Istanbul area, which has a population of 15 million. This hospital accepts new outpatients with or without doctor's referral. Therefore, one may think that the outpatient population may potentially reflect a general outpatient population in this hospital in Turkey, and the control group consisted of women with non-neoplastic and non-hormone related illnesses selected from the waiting area of different clinics. Although the study was not population-based, patients diagnosed and treated in a large Istanbul Medical Faculty Hospital were included that limited any potential biases related with the treatment. Furthermore, strength of this study is its relatively large size, which provided reasonably stable risk estimates.
The incidence of breast cancer increases with age, doubling about every 10 years until the menopause. McPherson et al reported that, of every 1000 women aged 50, two will recently have had breast cancer diagnosed and about 15 will have had a diagnosis made before the age of 50, giving a prevalence of breast cancer of nearly 2% . Vogel et al suggested that, the risk of breast cancer increases among women older than 50 years of age especially who have benign breast disease, especially those with atypical ductal or lobular hyperplasia . This study also showed that an age ≥ 50 year has effect on increased breast cancer risk significantly both in univariate and multivariable analyses.
Our study revealed that spontaneous abortion was associated with the decreased risk of breast cancer in univariate analysis whereas induced abortion was associated with increased breast cancer risk in both univariate and multivariable analyses. Some previous studies suggested that, induced or spontaneous abortions were associated with either increased or decreased risk of breast cancer, or no associations could be found with breast cancer risk for these factors [14–17]. Paoletti et al reported that a history of spontaneous abortion was not associated with breast cancer risk, although the risk was slightly increased with repeated miscarriages . That study also showed that spontaneous abortion was associated with decreased risk of premenopausal breast cancer followed by an increased risk of postmenopausal breast cancer . In the EPIC study, the relative risk of breast cancer of women who did not report any previous spontaneous abortions, was significantly found to be increased compared to those who reported two or more spontaneous abortions than for those reported one . In the Iowa cohort, the age adjusted risk among women who had experienced an induced abortion was 1.1 compared to those who never had an induced abortion . Furthermore, Michels et al found a positive association between induced abortion and breast cancer risk in women younger than 50, and a negative association in older women . Therefore, similar to our findings the majority of the studies reported that induced abortion was associated with increased breast cancer risk.
It was found that hormone replacement therapy (HRT) and oral contraceptive use were directly related to breast cancer risk in many epidemiologic studies [22–25]. Conversely, other studies reported that oral contraceptive use did not increase breast cancer risk [26, 27]. In the present study, we found that use of oral contraceptive use was associated with decreased breast cancer risk in both univariate and multivariable analyses whereas HRT was interestingly found to be associated with decreased breast cancer risk only in univariate analysis. However, these results were not dose and duration dependent. Therefore, further studies are required to test the consistency of our findings.
Tavani et al suggested  that older age at first birth (≥ 30 years) was associated with increased breast cancer, our results did support their data that being equal or more than 35 years of age at first birth is associated with increased breast cancer risk in univariate analysis. Late age at first birth delays terminal duct proliferation of mammary gland, and these women may have a higher proportion of epithelial cells that are susceptible to carcinogenic insult .
The most well established and documented data about endocrinological factors that decrease breast cancer risk are ever having breast fed and longer durations of breast feeding [3, 29–31]. Some studies showing a longer duration of breast feeding decreases breast cancer risk [30, 32]. Kim et al, suggested that average duration of breast feeding for 11–12 months reduced the breast cancer risk by 54% in Korean women as opposed to the duration of 1 and 4 months . Kuru et al  similarly showed that there was a significant association in Turkish women with breast feeding and decreased risk of breast cancer. Our data in univariate analysis also suggested that the association between decreased risk of breast cancer and breastfeeding. However, we could not find any relationship between the duration of breast feeding and risk of breast cancer.
Many studies suggest that the educational level is associated with increased risk of breast cancer [33–36]. Tavani et al  revealed that patients with breast cancer were significantly more educated (>13 years) than controls . This increased risk in these women may be due to the western life style in these women associated with HRT use or dietary changes or decreased exercise, or obesity or late age at first birth or decreased breast-feeding. Contrary to these findings, our study found that education (>13 years) was associated with decreased breast cancer risk in univariate analysis. These results may be due to some cultural differences based on the fact that educated Turkish women may be less affected by western life style compared to other women in the world or due the increased awareness for cancer screening etc.
The results of epidemiological studies of the association between cigarette smoking and breast cancer risk have been inconsistent [37–39]. Several recent analyses have suggested an increased risk of breast cancer among women who smoked cigarettes for a long period of time and/or who started smoking before their first pregnancy [38, 40–42]. Canadian National Breast Screening Study  reported that there was a statistically significant association between the duration of cigarette smoking (>40 years versus null, OR = 1.50), or the intensity of smoking (>40 cigarettes per day versus null, OR = 1.20), or the cumulative exposure (>40 pack-years versus null, OR = 1.17). Cigarette smoking appears to have antiestrogenic effects. Estrogen is well established risk factor of breast cancer. Since smokers have an earlier age at menopause , cigarette smoking might protect against breast cancer due to its antiestrogenic effects. In univariate analysis, our data also showed an inverse association between cigarette smoking and breast cancer risk. However, duration or intensity of smoking was not investigated in the current report that might be one of the weaknesses of this study. On the other hand, this finding should not be interpreted that women should be encouraged to smoke to decrease their breast cancer risk. It is well known that cigarette smoking has so many potential side effects associated with increased cancer risks for many other types of cancer such as lung cancer, or esophageal cancer, or laryngeal cancer etc.
One of the strongest risk factors for developing breast cancer is a family history of disease. In concordance with previous studies [44, 45], we also found an increased breast cancer risk associated with first-degree family history of breast cancer (mother or sister) in univariate analysis. Similarly, BMI equal or more than 25 was associated with increased breast cancer risk in both previous reports [46–51] and our current study in univariate analysis The association of increased breast cancer risk has been especially well established for young premenopausal women related to low physical activity, and anovulation in overweight and obesity [46–51].