Approximately 5 to 10 percent of all breast cancers are related to known mutations in susceptibility genes such as BRCA1 and BRCA2. As genomewide association studies continue to identify novel breast cancer risk loci, there has been a steady increase in genetic testing and in the number of annually performed risk-reducing operations. Although a clear survival benefit has been demonstrated for prophylactic mastectomy and salpingo-oophorectomy in patients with BRCA1 and BRCA2 mutations,[19,20] current guidelines do not address the order in which these procedures should be performed, and the existing literature is inconsistent with regard to the potential benefit of coordinated breast and gynecologic operations.
Here, we reviewed all cases of coordinated multispecialty breast and gynecologic operations performed between 2004 and 2019 at Stanford University Medical Center to compare postoperative outcomes to patients who had undergone separate operations. Patients who had undergone combined procedures developed postoperative complications related to breast surgery in 46.5 percent and to gynecologic surgery in 12.8 percent of cases, whereas separately performed operations carried lower complication rates of 19.0 percent for breast and 3.4 percent for gynecologic procedures (p < 0.001 and p = 0.08, respectively). We adjusted for a variety of potential confounders using a multivariate logistic regression model and found a significantly elevated risk for overall postoperative complications in cases of combined operations (OR, 5.87; 95 percent CI, 2.03 to 16.91; adjusted p = 0.02).
Several previous studies have reported on outcomes of coordinated breast and gynecologic operations; however, the majority of these studies are smaller case series, assessing the general feasibility of combined procedures, without statistical comparison of different treatment groups.[21–23] Ma et al. conducted a retrospective review of 73 cases of simultaneous breast and gynecologic operations performed at the authors' institution. Their descriptive case series reports an overall complication rate of 44 percent, which is similar to our data for combined procedures. Two independent studies have analyzed cases from the American College of Surgeons National Surgical Quality Improvement Program database and yielded conflicting results. Blau et al. extracted 2557 cases from the National Surgical Quality Improvement Program database based on postoperative International Classification of Diseases, Ninth Revision codes for prophylactic mastectomy and/or oophorectomy, among which 87 cases of combined breast and gynecologic operations were identified. The authors did not find significant differences in surgical-site infections, urinary tract infections, graft/prosthesis/flap failures, or length of hospital stay. Tevis et al. analyzed 135 cases of combined breast and gynecologic operations and 74 cases of combined breast, gynecologic and plastic surgical procedures extracted from the National Surgical Quality Improvement Program database. Their study found a higher rate of postoperative complications after combined operations involving breast, gynecologic, and plastic surgical procedures compared to breast operations alone; however, they do not provide details about the specific complications that occurred in these cases and did not control for confounding variables related to significant differences in patient comorbidities between the groups.
Overall postoperative complications after immediate breast reconstructions with tissue expander or abdominal free flaps in our study are in the range of previously published data.[25,26] We found a significantly higher rate of delayed wound healing and wound dehiscence and a trend toward higher overall complications in patients who had undergone immediate breast reconstructions with tissue expander combined with oophorectomy compared to patients with separate procedures (56 percent versus 12 percent overall complication rate). In the subgroup of patients with autologous flaps, overall complications occurred more frequently in patients who had undergone free flap operations combined with oophorectomy (48 percent versus 24 percent); however, statistical significance was missed, presumably because of a low sample size.
Our study is the first to compare two well-characterized cohorts of patients with comparable baseline and demographic characteristics for postoperative complications related to the timing of breast and gynecologic operations. Significantly higher rates of infections and delayed wound healing were found after combined breast and ovarian operations compared to separate procedures, which is consistent with the findings of the national database analysis by Tevis et al. Although patients with separate breast and ovarian procedures in our study had a significantly higher number of ovarian malignancies and longer cumulative procedure times compared to patients with combined procedures, this did not translate into a higher rate of postoperative complications related to the gynecologic surgery. Moreover, we did not find a delay of the start of adjuvant chemotherapy and radiation therapy in patients who underwent separate surgical procedures. While combining two surgical procedures under the same anesthesia may appear more efficient and satisfy a patient's desire to complete their prophylactic risk-reducing operations as soon as possible, our findings indicate a clear benefit in outcomes for patients who undergo separate breast and ovarian operations. The risks and benefits of single- versus two-stage procedures should therefore be given careful consideration during preoperative surgical planning and patient consultation. We hypothesize that combining two surgical procedures, one of which includes an intraabdominal procedure, in two separate anatomical areas, leads to an elevated stress response. Several studies have shown that an increased surgical stress response causes multisystem effects, including metabolic, neuroendocrine, immunologic, and hematologic changes, leading to an elevated risk for surgical-site infections.[27–30] Further studies will be required to confirm this hypothesis in patients undergoing combined breast and gynecologic operations.
Limitations of our study include its retrospective nature and the relatively small sample size. Therefore, further prospective studies investigating complication rates in patients with combined and separate breast and gynecologic operations are needed. Our data collection was performed with minimal selection criteria and we included all patients with combined and separate breast and gynecologic procedures between 2004 and 2019 performed at a single institution. To reduce the risk for observer bias in our study, comorbidities, demographic characteristics, and postoperative complications of our patients were collected by reviewers who were blinded for group allocation. Thus, we have reduced potential bias, which is inherent in any retrospective study, to a minimum and believe that our analysis accurately represents the postoperative outcomes in our patient cohort. Controlling for key confounders using multivariate logistic regression analysis allowed us to analyze the impact of combined breast and ovarian operations on postoperative complications with statistical robustness. Future studies should also aim to prospectively analyze the impact of specific combinations of oncologic and reconstructive surgical procedures on postoperative outcomes. Given the variety of oncologic and reconstructive surgical treatment options, which are tailored to individual breast cancer patients, prospective randomized controlled trials are hardly feasible.
Plast Reconstr Surg. 2022;149(5):1050-1059. © 2022 Lippincott Williams & Wilkins