Population impact of systematic underdosing of adjuvant chemotherapy in obese women

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Background and Objective: Obesity is associated with a higher risk of breast cancer recurrence, possibly due in part to systematic underdosing of adjuvant chemotherapy in heavy patients (Griggs et al., Arch Int Med 2005, Griggs et al, J Clin Oncol 2007, Colleoni Lancet 2005). Despite extensive literature supporting the use of full weight-based doses in overweight women, up to 40% of heavy women are given substantially reduced doses of chemotherapy. These dose reductions, not accounted for by comorbidity, age, or severity of disease, increase the risk of breast cancer relapse and death, particularly in women with estrogen receptor (ER)-negative disease (Colleoni Lancet 2005). The practice of dose reducing in obese patients has important implications for racial, ethnic, and social disparities in breast cancer outcomes given the higher prevalence of obesity and ER-negative disease among some minority groups and among women with lower socioeconomic status (SES). The purpose of this study was to estimate the population impact of unwarranted chemotherapy dose reductions. Methods: Using published studies we estimated the number of women diagnosed with breast cancer each year in the U.S., the proportion of tumors that are ER-negative, the proportion and number of obese patients receiving chemotherapy, the proportion receiving reduced chemotherapy doses, and the absolute risk reduction (ARR) of full chemotherapy dosing over reduced chemotherapy dosing. The number of recurrences not prevented (NNP) was calculated using the following formula: NNP = (Number obese patients receiving chemotherapy x Proportion receiving reduced doses)/NNTb, where the NNTb (number needed to treat to benefit one person) is equal to 1/ARR. Sensitivity analyses were performed by varying the estimates over a wide range of values. Results: Using published findings of chemotherapy dosing patterns over a wide range of the variables in the equation, we estimated that between 1,533 and 6,132 women diagnosed with breast cancer each year in the U.S. will ultimately experience a recurrence that could have been prevented with optimal, full weight-based chemotherapy dosing. As the prevalence of obesity increases, the population impact of underdosing will likewise increase. A substantial proportion of underdosed obese women are likely to be racial/ethnic minorities or of lower socioeconomic status. Conclusion: Improving the quality of chemotherapy in patients who have been advised to and have agreed to receive chemotherapy is likely to improve breast cancer outcomes at the population level. Black women, Hispanic women, and women with lower socioeconomic status may be particularly likely to benefit from efforts to improve chemotherapy quality given the higher likelihood of ER-negative disease and higher stage at presentation as well as a concentration of obesity in these populations.