Treatment-related factors

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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