Sequencing of Therapy in Breast Cancer

Abstract

33Breast cancer is the most common female malignancy in Europe and North America, and represents a heterogeneous group of proliferative lesions, the prognosis of which depends on a host of interrelated factors including draining axillary lymph node status, tumor size, grade, mitotic index, and molecular profile. The treatment of breast cancer is multimodal, and can include surgical management, chemotherapy, radiation, and hormonal modulation. The selection and sequencing of the different facets of treatment are based on patient and tumor variables, including prognostic scores and axillary or distant metastases. Indications for Radiotherapy in Breast CancerRadiation therapy in breast cancer is indicated in all patients undergoing breast conservation, and postmastectomy in patients with T3 or T4 tumors, or with four or more positive axillary nodes. [1][2][3][4] The role of radiotherapy in breast cancer management has undergone overwhelming changes since its initial application. Its utility was highest in the pre-screening era when women often presented with advanced stage breast cancer or positive axillary disease. Technique-related cardiac complications precipitated a decline in its application, but technical improvements have facilitated its integration into standard management regimes. The aim of radiotherapy in breast cancer care is to reduce the risk for loco-regional recurrence, thereby conferring a survival advantage. Local recurrence is associated with higher rate of distant metastasis and death. Radiation of the chest wall post mastectomy has also been associated with survival benefit in patients with node-positive disease 5,6 and has been shown to greatly reduce the risk for local recurrence or chest wall failure. 5 A large review has shown that for every four local recurrences prevented, one death from breast cancer is avoided over the subsequent 15 years. 5 Postmastectomy radiotherapy also has been shown to confer a survival benefit to nodepositive patients at lower risk for recurrence. The British Columbia trial showed greater relative reduction in patients with only one to three involved axillary nodes compared with those with more than four positive nodes. The role of irradiation of the breast in breast-conserving surgery is well established as it is associated with significant reduction in the rate of local recurrence as well as breast cancer deaths, by virtue of eradication of any residual microscopic disease at the surgical margins. 7 Loco-regional and distant disease-free survival benefit has been noted in patients undergoing breast conservation followed by radiotherapy, 8 and some groups therefore recommend the use of radiotherapy in the majority of patients with nodepositive disease, regardless of nodal burden. 9 Postmastectomy irradiation has been shown to be particularly beneficial in patients with triple negative breast cancer, a cohort that has been previously identified as bearing an inflated risk for loco-regional recurrence irrespective of nodal status. 10In cases of breast cancer we te...