Hadjisavvas et al. BMC Cancer 2010, 10:447 http://www.biomedcentral.com/1471-2407/10/447 associated with single women may possibly be due to nulliparity. Many studies have examined the association between body mass index (BMI) and breast cancer incidence. It was observed that in postmenopausal women, obesity (BMI > 30 kg/m2) was associated with about 50% increase in breast cancer risk when compared with lean women (BMI 20 kg/m2). This association was not observed in premenopausal women. In contrast, in some studies it was observed that during the premenopausal years, breast cancer risk was slightly lower in obese women [18]. In our study, no information on meno- pause status at the time of diagnosis was available. By comparing BMI at the time of interview between cases and controls, no statistically significant differences were observed between the two groups. The relationship between BMI and breast cancer risk is complex and is better assessed in prospective studies where further anthropometric data are accurately collected at baseline and at regular intervals afterwards. In this context, no conclusive results regarding the association between BMI and breast cancer incidence in the Cypriot popula- tion can be drawn on the basis of this study. Family history of breast cancer is one of the most well established, widely accepted risk factors for this disease. Having one first-degree relative with breast cancer approximately doubles a woman’s risk for developing breast cancer. The risk is elevated significantly by increasing the number of affected relatives [19,20]. Our findings are in accordance with other published studies and suggest that a positive family history of breast can- cer is one of the most significant risk factors for this disease in Cyprus. In fact, if women with positive family history of cancer are more likely to attend mammogra- phy clinics for screening, the observed association may actually be an underestimation. Breast cancer risk is associated with several reproduc- tive factors. It is well established that breast cancer risk increases with early age at menarche [21-23]. This asso- ciation is consistent with the hypothesis that breast can- cer risk is related to the extent of breast mitotic activity. This activity is driven by estrogen and progesterone exposure during the luteal phase of the menstrual cycle [24], which determines the probability of tumorigenic somatic events [25]. Therefore, an early age at menarche increases the period during which the breast is mitoti- cally active and subsequently increases breast cancer risk. Similarly to previous investigators, we observed that an early age at menarche is associated with an ele- vated risk of breast cancer in our population. The effect of breastfeeding on breast cancer risk has been controversial indicating either no association, or a weak protective effect against breast cancer [26]. Studies in countries with a long duration of breastfeeding have Page 8 of 10 reported substantial protective effects, whereas a num- ber of studies in Western populations failed to detect an association, possibly due to the low prevalence of pro- longed breastfeeding [26]. A meta-analysis of breastfeed- ing and breast cancer risk, by the Collaborative Group on Hormonal Factors in Breast Cancer, showed that increasing duration of breastfeeding confers a protective effect on breast cancer risk, over and above that already known to be afforded by parity itself [27]. Breastfeeding is hypothesized to reduce the risk of breast cancer pri- marily through two mechanisms, differentiation of breast tissue [28] and reduction of the lifetime number of ovulatory cycles [29]. The results of our study suggest an inverse association between breastfeeding and breast cancer risk, even though a dose-response relationship with self-reported duration of breastfeeding was not observed, possibly a result of misclassification. This find- ing is consistent with the results of the large collabora- tive study showing breastfeeding to be protective for breast cancer [27]. Breastfeeding is one of the few potentially modifiable factors that can reduce breast cancer risk. Further investigations are warranted in order to understand the underlying mechanisms of the protective effect of breastfeeding and how protection might be conferred. Once these are determined, inter- ventions, which would mimic breastfeeding, could be developed for the benefit of women who have never breastfed [27]. Surprisingly, we observed an inverse association between hormone replacement therapy (HRT) and breast cancer risk. Results from randomized controlled trials and from observational studies have shown that use of HRT increases breast cancer risk. Furthermore, the effect of HRT on breast cancer risk depends also on the different combinations of HRT as well as on the duration of usage [30-34]. Overall, studies have con- cluded that oestrogen-progestagen combinations increase the risk of breast cancer, and that the risk was elevated, in women who were treated for at least 5 years [32,34]. The above results should be interpreted with caution due to the difficulties experienced by Cypriot women in recalling information regarding type and exact duration of HRT use. However, there is no reason to believe that such recall was differential among cases and controls. Unlike other studies [34,35], the vast majority of women in our sample reported never having used HRT while only a small percentage of women in our sample reported use for periods longer than 5 years (e.g. 7.8% among healthy controls). Furthermore, while in prospective studies one would expect to find an asso- ciation between HRT use and breast cancer risk, in our retrospective study it is not surprising to observe an inverse association. It is very likely though that cases, once diagnosed with breast cancer, were not prescribed