Treatment of Breast Cancer in the Diabetic Patient

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Several of the well-known complications of diabetes, including nephropathy, neuropathy, heart disease, impaired wound healing and tendency to infections can adversely affect all forms of cancer therapy: surgical, radiation, chemotherapy and even hormonal therapy.

Diabetes and Surgery for Breast Cancer

Diabetes is associated with increased risk of complications following breast cancer surgery. Analysis of 326 patients revealed a strong association between diabetes and wound infection following breast surgery: wound infection occurred in 12 of 264 (5%) non-diabetic patients but in 6 of 44 (14%) of the diabetic patients [48]. Diabetes is also associated with ipsilateral upper arm dysfunction 5 years following mastectomy [49].

Diabetes and Radiation Therapy for Breast Cancer

Data regarding efficacy and complications of radiotherapy for breast cancer are limited. However, diabetes is associated with increased risk of early and late complications of radiation. In patients treated for cervical cancer, diabetes was associated with formation of recto-vaginal fistula and bowel obstruction and, in elderly patients with prostate cancer given radiotherapy, with early and late gastrointestinal and genitourinary complications. Analysis of 828 patients treated with breast-conserving surgery and radiotherapy identified diabetes as an independent risk factor for post-treatment myocardial infarction [50]. An analysis of 246 women treated with postmastectomy radiotherapy did not identify diabetes as an independent risk factor for skin complications. However, only 19 diabetic patients were included in the analysis [47].

Diabetes and Chemotherapy for Breast Cancer

To our knowledge, no study has reported about the specific complications of chemotherapy in patients with breast cancer and diabetes. In a study of 33 patients with ovarian cancer and diabetes who were given cisplatin or paclitaxel, 21 (64%) had neurological symptoms and exacerbation of hyperglycemia; treatment changes were needed in 5 patients. Another study reported on the toxic effects of fluorouracil in 7 patients with diabetes that was poorly controlled; however, neither of these studies included a control group. Diabetes may accentuate other side effects and complications of cancer chemotherapy. For example, patients with diabetes who have peripheral neuropathy are more prone to complications of vinca alkaloids or tax-anes, and those with diabetic cardiomyopathy are probably more susceptible to complications from cardiotoxic medications such as doxorubicin and trastuzumab (herceptin). The possibility of severe complications from infection should also be considered.

Diabetes and Hormonotherapy for Breast Cancer

Adverse interactions between hormone therapy and diabetes are probably uncommon. Tamoxifen is a selective ER modulator, which is commonly used for the treatment of breast cancer in the adjuvant, as well as metastatic setting. Tamoxifen use is associated with an up to 4 times increased risk of endometrial cancer, and several studies have also reported an up to 1.5 times increased risk of endometrial cancer in patients with diabetes. However, no evidence suggests an enhanced risk of endome-trial cancer in patients with diabetes who were treated by tamoxifen compared with those without diabetes. Acute pancreatitis due to severe hypertriglyceridaemia after tamoxifen treatment in patients with diabetes has been described, but the frequency of this side effect is not known and is probably very low. Raloxifene is another selective ER modulator, which is used to treat osteoporosis and has also been shown to prevent breast cancer in high-risk populations. In a small randomized study of 39 postmenopausal diabetic women, raloxifene administration slowed progression of albuminuria [51]. It is currently unknown whether tamoxifen treatment has a similar beneficial effect. At present, there is no evidence for an interaction between aro-matase inhibitors and diabetes.

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