Treatment-related factors

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Surgery
Obesity is associated with the need for more extensive axillary surgery in women with breast cancer, as the success of sentinel lymph node biopsy is inversely related to BMI ^[41].

Radiotherapy
Obesity is associated with an increased incidence of radiotherapy complications, such as lymphedema of the arm and breast.

A review of the literature addressing lymphedema as a complication of radiotherapy confirmed that this adverse event is more common in patients who are obese ^[42].  Uniform radiation dose delivery in obese women with large breasts is technically challenging; therefore, reduction mammoplasty has been recommended in women with very large breasts in order to maximize the benefit of adjuvant radiotherapy ^[43].

Chemotherapy
It has been postulated that systematic undertreatment of breast cancer in obese women contributes to the poorer prognosis of these women compared with those of normal weight ^[44].  Chemotherapy dose reduction is associated with a high likelihood of treatment failure, as shown in the CALGB (Cancer and Leukemia Group B) 8541 study, which included 1471 women ^[45].  However, obesity is still associated with a poor prognosis in patients who receive optimum dose chemotherapy. After adjusting for other factors, the RR of disease recurrence among obese patients after adequate chemotherapy has been found to be 1.33 (95% CI 1.05–1.68) compared with non-obese women ^[46].

There is indirect evidence suggesting that chemotherapy is less efficient in obese women, as leukocyte nadir counts remained high in obese women in a study considering blood leukocyte count as a surrogate marker of chemotherapy efficiency ^[47]. In addition, it takes longer for obese women to develop amenorrhea from chemotherapy, which may be a sign of increased aromatization of peripheral androgens, making the endocrine component of chemotherapy less effective ^[48,49].

Endocrine treatment
Some investigators have suggested that due to increased aromatization of peripheral androgens into estrogens, antiestrogen treatment may be less effective in obese women ^[50]. Obese women have significantly higher levels of plasma estrogen than nonobese women, suggesting that peripheral aromatization may curb complete ovarian suppression in obese women.  The efficacy of tamoxifen has been shown to be equal in obese and non-obese women with node-negative, ER-positive breast cancer ^[51].

Biological treatment
To date, there is no published evidence indicating that overexpression of human epidermal growth factor receptor-2 is more common in obese women than the general breast cancer population ^[52].

Amtul R Carmichael, MD
Russells Hall Hospital, Dudley, UK

References

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