Hadjisavvas et al. BMC Cancer 2010, 10:447 http://www.biomedcentral.com/1471-2407/10/447 A. Pregnancy No Yes Breastfeeding1 No Yes Breastfeeding by duration1, 2 Never ≤6 months 7-12 months >1 year B. Breastfeeding No Yes Number of children None One Two Three 1.00 0.69 (0.49,0.97) 1.00 0.69 (0.57,0.82) 1.00 0.71 (0.58,0.88) 0.76 (0.58,0.98) 0.61 (0.48,0.77) 1.00 0.69 (0.57,0.83) 1.00 0.90 (0.59,1.37) 0.84 (0.61,1.15) 0.68 (0.49,0.94) Table 2 Odds Ratios of breast cancer risk in terms of A) pregnancy and breastfeeding (either status or duration) and B) breastfeeding and number of children before and after adjusting for the effect of each other and all other risk factors in multivariable logistic models Before adjustment OR (95%CI) After mutual adjustment p-value OR (95%CI) p-value Page 5 of 10 p-value 0.79 <0.01 0.043 <0.01 0.87 0.54 <0.01 <0.0013 0.253 Fully adjusted4 OR (95%CI) 1.07 (0.66,1.72) 0.72 (0.59,0.90) 0.73 (0.57,0.93) 0.86 (0.64,1.16) 0.68 (0.51,0.91) 1.29 (0.76,2.18) 1.27 (0.76,2.18) 1.14 (0.82,1.99) 0.03 0.89 (0.62,1.28) <0.001 0.63 (0.45,0.89) <0.0013 0.03 <0.013 0.65 (0.45,0.94) 0.69 (0.47, 1.03) 0.56 (0.38,0.81) 1.06 (0.69,1.64) 1.04 (0.74,1.48) 0.90 (0.62,1.29) 0.72 (0.58,0.88) <0.01 0.72 (0.58,0.90) Notes: 1In the adjusted models, odds ratio refers to the combined effect of pregnancy and breastfeeding, status or duration respectively, as estimated in a model with an interaction term between the two variables but no main effect for breastfeeding. 2p-values of Likelihood Ratio Test comparing the goodness of fit of model including breastfeeding duration Vs simpler model with breastfeeding expressed as binary variable = 0.27, 0.19 and 0.33 respectively, indicating no better fit of full model. 3P-value for trend across ordered categories. 4Due to collinearity, the variables pregnancy and number of children were mutually excluded from the fully adjusted models. breastfed at all while only 10% of them breastfed for longer than 6 months. In contrast, amongst women with 3 or more children, only 15% did not breastfeed while as many as 38% reported breastfeeding for at least one year. The Kendall’s tau-b was 0.42, p-value for independence < 0.001, indicating a relatively strong and statistically significant correlation between breast- feeding duration and number of children. Considering every possible pair among the participants, this non- parametric measure is calculated on the basis of the number of occasions where the ranking of both breast- feeding duration and number of children are in the expected direction (i.e. a higher rank in one variable is accompanied by a higher rank in the other) as com- pared to the number of discordant pairs. The strong univariable association observed with number of chil- dren attenuated once breastfeeding was controlled for in the multivariable logistic analysis while not much change was observed in the case of breastfeeding. This cannot be simply a result of collinearity as the confi- dence intervals also remained largely unaffected, more likely indicating that the observed association with number of children was confounded by the effect of breastfeeding. In fact, this is also supported from the results of the stratified analysis where the estimate for the odds ratio for a one unit increase in the number of children was 0.92 (95%CI 0.80-1.05) among women who did not breastfeed and 0.97 (95%CI 0.82-1.15) among women who breastfed. The Mantel-Haenszel estimate control- ling for breastfeeding is 0.94 (95% CI 0.85, 1.04) and test of homogeneity of ORs = 0.61, indicating no evi- dence of effect modification in the relationship of breast cancer and number of children by breastfeeding status. Further adjusting for other variables revealed no associa- tion with parity while interestingly wide confidence intervals were observed. On the other hand, the effect estimate of breastfeeding (and the confidence intervals for that matter) practically remained unchanged at 0.72 (95%CI 0.58, 0.90). Table 3 presents odds ratios (and 95% CI) for breast cancer in terms of each participant characteristic before and after adjusting for the effect of all other in a multi- variable model. On the basis of the results presented above, breastfeeding was included as a binary variable while parity was not considered further in the multivari- able models. The strongest associations were observed with family history of breast cancer, age at menarche