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About two-thirds of women with breast cancer have hormone receptor-positive breast cancer, and hormonal therapy is recommended following surgery. For post-menopausal women, aromatase inhibitors (AIs) are now the preferred class of therapy, as they outperform tamoxifen with 3%-5% fewer recurrences seen, even though a difference in the death rate has not been observed.A series of studies was presented at the San Antonio Breast Cancer Symposium on Thursday that attempted to discern if there are any factors that might allow us to better individualize treatment recommendations in this situation.One of larger studies, called the TEAM trial, compared the sequence of tamoxifen followed by the AI Aromasin (exemestane) to Aromasin for five years. This trial had already shown that these regimens are equivalent in terms of recurrence risk, but in this analysis, the presence of the family of growth factor receptors known as HER1, HER2 and HER3 was associated with a higher risk of recurrence regardless of the regimen used, so it did not help doctors and patients decide which regimen would be best.Another sophisticated trial looking at multiple genes expressed over time in the tumors of patients receiving the AI Arimidex (anastrozole) suggested that inflammation and immune reactions might predict a lower chance of response to therapy. Dr. Dunbier from the Royal Marsden Hospital in London speculated that such an immune reaction in the breast, sometimes seen by the pathologist as white cells "infiltrating" the tumor, might activate growth signals. While this finding is too early to apply in the clinic, it might shed some light on the biology of why some tumors are more aggressive and might require other therapies, even immune therapies; this may lead to focused trials in this area.Another series of trials attempted to look at rare side effects of AIs. We have witnessed situations in medicine where rare side effects, such as heart attacks associated with the nonsteroidal pain drug Celebrex (celecoxib), were not picked up until years after the drug was approved. So it is important to continually examine these side effects over time. With AIs, there was a suggestion that the risk of heart attack might be slightly elevated. One study attempted to look at "real life" use of hormonal therapy by examining insurance claims and pharmacy data on 44,000 women with breast cancer and 44,000 women without breast cancer who were matched for age and other characteristics. There did not appear to be a difference in heart attacks with either tamoxifen or AIs, and there was a decreased stroke rate with either hormonal therapy in all breast cancer patients, a finding that has been observed before. Bone fractures were more common with AIs--again, something that was already known. Another analysis looked at pooled data from several trials comparing tamoxifen to AIs and was able to detect very small increases in certain risks; for example, cardiac side effects were seen in 4.2% of patients on AIs and 3.4% of patients on tamoxifen, a difference of 0.8%. These small differences could not be picked up in individual trials. These risks can also be expressed as the number of patients you would need to treat to see one additional harmful event of an AI compared with tamoxifen--in the case of a cardiac event (like heart attacks), that would be 132 patients. This analysis also showed more bone fractures with AIs (7.5%) compared to tamoxifen (5.2%), or one extra fracture for every 46 patients treated. More uterine cancers were seen with tamoxifen, but very low rates overall--0.5% with tamoxifen and 0.1% with AIs, or one additional case for every 250 patients treated. These types of numbers are useful for making any medical decision and weighing the benefits (less recurrence risk) versus the risks in a numerical way. When we think of personalized medicine, it is also about making tailored benefit/risk analyses; that's why these "meta-analyses" are important.