Each improvement in breast cancer treatment has had a significant impact on the timing and approach to breast reconstruction. The most important of these is the changing status of radiation therapy in the breast cancer treatment system. In the early 1980s, local radiation therapy was not considered to improve the survival of breast cancer patients and was therefore rarely used [1-8]. During this period, the use of breast-conserving surgery and immediate breast reconstruction gradually increased. However, since 1990, a series of randomized controlled trials have shown that postoperative radiotherapy is effective in reducing local recurrence rates and improving survival in patients with early-stage breast cancer [9-10]. Guided by this view, the use of postoperative radiotherapy has become increasingly popular among patients with early-stage breast cancer, who are also the primary targets for immediate breast reconstruction. This change in the treatment of breast cancer necessitates an adjustment in the choice of method and timing of breast reconstruction. How does radiation therapy interact with immediate breast reconstruction? How should we respond? In this article, we will review and analyze the relevant literature on these two issues. 1. Indications for postoperative radiotherapy for breast cancer In 1997, the results of a randomized controlled trial conducted in Denmark [9] and Canada [10] were published in the New England Journal of Medicine. The results of this landmark study showed that postoperative radiotherapy could reduce the local recurrence rate of early-stage breast cancer patients. Since then, the use of postoperative radiotherapy in early-stage breast cancer patients has become increasingly common. Almost all authoritative guidelines for postoperative radiotherapy for breast cancer (e.g., American Society of Clinical Oncology ASCO) now recommend postoperative radiotherapy for patients with “T1 or T2 with four or more axillary lymph node metastases” and “tumor diameter ≥5 cm”[11] . . Many institutions also recommend active consideration of postoperative radiotherapy for patients with one to three positive lymph nodes. The effect of radiotherapy on reconstructed breast Several authors have compared the postoperative radiotherapy group with the group without postoperative radiotherapy after breast reconstruction and found that the complication rate was significantly higher in the postoperative radiotherapy group than in the group without postoperative radiotherapy. These studies involved the application of various breast reconstruction procedures such as prosthesis, TRAM flap, and DIEP flap. Complications that occurred included periosteal contracture, prosthesis exposure, infection, fat necrosis, skin wrinkling, and flap contracture. In 1997, Williams et al. conducted a retrospective study of three groups of patients [12]: those who underwent postoperative radiotherapy after breast reconstruction with a TRAM flap (19 cases), those who did not undergo postoperative radiotherapy after breast reconstruction with a TRAM flap (572 cases), and those who underwent postponed breast reconstruction after completion of postoperative radiotherapy (108 cases). In the postoperative radiotherapy group, 52.6% of the patients had significant flap changes, and 31.2% of the patients required reoperation for repair. In 2000, Spear et al. conducted a retrospective study of 40 patients who underwent postoperative radiotherapy after saline breast reconstruction and 40 patients who underwent the same surgical approach without postoperative radiotherapy [13] and found that the complication rate in the postoperative radiotherapy group was significantly higher than that in the control group (52.5% versus 10%, P<0.001), and about 2/3 of the postoperative radiotherapy group developed symptomatic periosteal contracture, whereas none of the control group developed periosteal contracture. In the control group, there was no case of pericardial contracture. In 2001, the University of Texas M.D. Anderson Cancer Center reviewed 32 cases of immediate postoperative breast reconstruction with a TRAM flap followed by postoperative radiation therapy versus 70 cases of delayed breast reconstruction with a TRAM flap after completion of postoperative radiation therapy [14]. The results showed that although there was no significant difference in the incidence of early flap complications (e.g., vascular obstruction, partial or total flap necrosis) between the two groups, the incidence of long-term complications (fat necrosis, flap atrophy, contracture) was significantly higher in the immediate reconstructed group than in the delayed reconstructed group (87.5% versus 8.6%, P<0.001). Up to 28% of patients in the immediate breast reconstruction group required reoperation or even additional flaps to repair the severe flap contracture and deformity caused by radiation therapy. In 2002, Rogers et al. compared 30 patients who underwent postoperative radiotherapy after breast reconstruction with a DIEP flap and 30 patients who underwent the same procedure without postoperative radiotherapy [15] and found that the complication rate was significantly higher in the postoperative radiotherapy group than in the control group. The complications that occurred included fat liquefaction (23.3% vs. 0%, P<0.001), fibrosis with skin wrinkling (56.7% vs. 0%, P<0.001), and flap contracture (16.7% vs. 0%, P<0.001). Theories of the mechanism of radiation therapy injury formation include the microvascular obstruction theory and the chromosomal variation theory due to direct cellular injury [16]. Recent studies have mostly supported the latter [17]. Electron microscopic studies of radiation-injured skin in humans [18] and animals [19] revealed only sporadic microvascular embolism, but revealed widespread permanent damage to fibroblast ultrastructure (e.g., mitochondria, rough endoplasmic reticulum, nuclei, etc.) in the affected areas, which persisted decades later [18-19]. Radiotherapy can cause fibroblast and fibroblast stem cell damage and delay wound healing and the survival of flaps and pieces of skin by blocking stem cell replication and neovascularization [14-16]. 3. Effect of breast reconstruction on radiotherapy Immediate breast reconstruction can have a detrimental effect on postoperative radiotherapy exposure field design [20-21]. An immediate controlled trial showed that postoperative radiotherapy to the medial lymph node area of the breast significantly improved survival [22-23]. However, the slope formed next to the sternum after breast reconstruction can affect the accuracy of radiotherapy in this area, resulting in an inadequate dose of radiotherapy to the medial lymph node region of the breast or excessive radiation side effects to the adjacent tissues (especially the heart and lungs).