In this analysis of the ACS-NSQIP database, we confirmed the findings from prior studies demonstrating that wound complications after breast cancer surgery are infrequent (≤ 4%). Wound complication rates do vary by type of surgical procedure performed, with the lowest rates observed after BCS (1.9%) and the highest after mastectomy with reconstruction (4.0%). As expected, factors associated with wound complications also varied by type of surgical procedure. For patients undergoing BCS, age, obesity, functional dependence, and undergoing a concurrent axillary lymph node dissection were associated with increased risk. For patients undergoing mastectomy, factors differed. Some of the observed factors, such as obesity, smoking, and hypertension, have been noted in prior studies (6, 13)
. However, we also identified functional dependence and diabetes as increasing risk; these factors have not previously been reported. However, regardless of type of surgery received, use of neoadjuvant chemotherapy did not significantly increase the risk of wound complications.
Concern regarding the theoretical increased risk of wound complications after the receipt of neoadjuvant chemotherapy has existed within the breast surgery community for some time. In response to early concerns, MD Anderson Cancer Center developed a protocol regarding timing of surgery for recipients of pre-operative chemotherapy. Under their “strict operative criteria”, all patients treated with neoadjuvant chemotherapy had to have a resectable tumor, white blood cell count greater than 2500 cells/mm3
, and platelet count greater than 50,000 cells/mm3
prior to mastectomy (9)
. This early single-institution study demonstrated that post-mastectomy morbidity in patients who received pre-operative chemotherapy was no different from patients who did not have pre-operative chemotherapy. Since that time, several studies have reported similar findings (8–11, 14)
; in these studies, “strict operative criteria” as reported by the MD Anderson group were not required. The findings of our study further corroborate the conclusions of these single-institution, retrospective studies.
Recently, there has been growing interest in outcomes after neoadjuvant chemotherapy and mastectomy with immediate reconstruction. Two single institution studies of patients who underwent mastectomy and immediate reconstruction found no significant difference in complication rates between patients who received neoadjuvant chemotherapy and those who did not (8, 11)
. Although we did not identify a statistically significant association between receipt of neoadjuvant chemotherapy and wound complications after mastectomy with immediate reconstruction, a trend was observed. This is noteworthy given the selection bias apparent in our patients undergoing immediate reconstruction after neoadjuvant chemotherapy. Patients selected for immediate reconstruction after neoadjuvant chemotherapy were younger and overall “healthier” than those who underwent mastectomy alone. Despite this, a trend towards increased wound complications after neoadjuvant chemotherapy and immediate reconstruction was noted. This may be a direct result of the chemotherapy received. However, other clinical data unavailable in the ACS-NSQIP dataset, including cancer stage and receipt of post-mastectomy radiation, may also impact patients’ risk of wound complications. Given the available data, we cannot conclude that expanding the use of immediate reconstruction to all patients who undergo neoadjuvant chemotherapy would be acceptable. However, our data does support the conclusion that neoadjuvant chemotherapy recipients selected by their surgeons to be a good candidate for immediate reconstruction can be expected to have good post-operative outcomes.
Several limitations exist for our study. First, patients in our study were not randomized to either timing of chemotherapy or to type of surgery performed, and as a result selection bias inevitably exists. Differences between the patient groups were evident for a number of factors, including age and co-morbidities, and multivariable logistic regression was used to adjust for this. Other variables relevant to patient selection, such as cancer stage, were not available in our dataset and remain unaccounted for in this analysis.
Additionally, the sampling strategy utilized by the NSQIP under-samples patients undergoing BCS compared to mastectomy; this is reflected in our BCS rate of 31%, which is lower than what has been reported for the United States population (15, 16)
. However, because we are not reporting on rates of surgery, but rather complications according to surgery type, this difference should not impact the conclusions of our study. Similarly, our reported rates of wound complications are lower than complication rates reported in other series (8, 10)
especially after breast reconstruction; this likely relates to the definitions of complications used. As the ACS-NSQIP is a quality improvement program largely designed to evaluate outcomes after general and vascular surgery, disease specific complications that would be relevant to breast cancer surgery (such as seroma aspiration or delay of chemotherapy) are not collected. This likely explains the difference between the rates reported in our study and other single-institution series.
Next, it is possible that our cohort of neoadjuvant chemotherapy recipients is incomplete. In the ACS-NSQIP, chemotherapy received in the 30 days prior to surgery is recorded and this variable was used to define our neoadjuvant cohort. It is possible that some neoadjuvant patients had a longer interval between the end of chemotherapy and surgery, and therefore may have been misclassified. Currently, no standard exists for the optimal interval between chemotherapy and surgery. However, one recently published randomized controlled trial described surgery between 14 and 28 days after chemotherapy (2)
and another study reported a median 27 day interval (9)
. This suggests that the majority of our cohort was appropriately categorized.
Finally, we were underpowered to detect small differences in wound complication rates; over 60,000 neoadjuvant chemotherapy patients would have been required to achieve a power of 80%. However, wound complication rates were low, even for the group who underwent mastectomy with reconstruction. We therefore believe that a clinically meaningful difference is unlikely to be observed with additional patients.
Although limitations exist to our study, these results currently represent the most comprehensive evaluation of neoadjuvant chemotherapy and post-operative wound complications following the surgical treatment of local-regional breast cancer. By using the ACS-NSQIP database, we were able to examine the outcomes from a multi-institutional cohort representing a range of community and academic surgical practices. Additionally, we had the benefit of prospectively collected and validated pre-operative and operative variables; this allowed us to control for both previously described risk factors for wound complications (including obesity, smoking, axillary dissection, and mastectomy) (6, 13, 17, 18)
as well as other unique factors. One of the greatest strengths of our study, however, is the rigorous methodology applied to collection of post-operative complications by the ACS-NSQIP. This increases the reliability and validity of our conclusions.