Introduction 1 2 3 3 3 4 5 6 7 8 9 10 13 14 15 16 18 19 21 20 22 Possible impact of treatment on common co-morbidities 21 23 26 25 Bone disease 27 28 29 31 32 33 34 34 35 34 34 36 37 39 38 1 35 40 41 Fig. 1 35  Aromatase inhibitors and bone disease 39 P P 39 Anastrozole 42 P 43 P P 44 P 42 45 46 P P 42 43 45 46 12 12 12 13 Letrozole P 8 10 P 10 P P 47 Exemestane 48 49 P P 50 51 P 52 P 11 P 53 54 P 52 55 P 11 Comparative studies of aromatase inhibitors 56 P 20 57 Bisphosphonates 20 58 59 60 61 T 60 62 62 63 62 61 Lipid metabolism: 64 65 66 67 68 Aromatase inhibitors and lipid metabolism Anastrozole P 42 P 13 68 P Letrozole 8 69 67 8 42 Exemestane 11 52 70 P P P P P Aromatase inhibitors versus placebo 10 n n 71 P P 50 Comparative studies of aromatase inhibitors 1 72 P P 72 Table 1 72 Percentage change from baseline n n P n P Total cholesterol  Week 12 −2.3 −3.8 0.617 −5.5 0.262  Week 24 +0.4 −0.0 0.900 −3.9 0.164  Triglycerides       Week 12 −2.9 +9.6 0.037 −7.7 0.417  Week 24 +0.3 +5.4 0.550 +2.1 0.827 Ratio of LDL-C:HDL-C  Week 12 −0.0 −3.1 0.486 +8.8 0.048  Week 24 +4.6 +3.4 0.847 +17.0 0.047  Non-HDL-C       Week 12 −2.7 −4.2 0.667 −3.5 0.820  Week 24 +1.3 +1.2 0.975 −0.6 0.630 Ratio of apo B:apo A1  Week 12 −1.0 −3.3 0.452 +4.4 0.069  Week 24 +0.0 −0.8 0.842 +9.0 0.023 LDL-C HDL-C apo B apo A1 Cardiovascular disease 73 77 75 73 78 79 80 81 82 88 89 90 Tamoxifen and cardiovascular disease 89 91 92 93 94 2 Aromatase inhibitors and cardiovascular disease 8 95 Anastrozole P P P 42 P 42 96 Letrozole P 8 97 Exemestane P 11 P 11 98 99 Aromatase inhibitors versus placebo P 10 10 Gynecologic health 100 102 29 103 104 105 109 110 115 116 117 Aromatase inhibitors and gynecologic health Anastrozole P 9 P 42 118 P 119 P 42 P P P P 120 P Letrozole 8 P P P P 121 P P 10 Exemestane P 11 P 52 P 52 122 P 11 Other adverse events Secondary cancer 4 42 8 11 93 Gastrointestinal health 123 P 42 Neurologic effects and visual disturbance 124 125 126 127 52 Dry mouth P 42 Cosmetic effects 64 P 128 118 129 130 P p 42 Quality of life and patient preference Anastrozole 118 131 118 131 P P P 132 Letrozole 10 8 121 133 2 134 134 Fig. 2 A P B P 133  Exemestane 135 P Conclusions 8 11 20 57 136 137 136 8 52 95 138 20 20 In conclusion, the efficacy benefits of AIs outweigh the risks when AIs are used as adjuvant therapy in postmenopausal women with early breast cancer. Safety, QOL, and patient preference must all be considered in the determination of the optimal strategy for long-term endocrine therapy, bearing in mind that patients may require treatment for 10 years or more. Every patient is unique, and endocrine therapy must be individualized according to clinical, biologic, and patient factors such as lifestyle, the presence of significant co-morbidities, and use of concomitant medications. Tolerability should no longer be an obstacle to effective, long-term endocrine therapy.