Endoscopy-assisted nipple-sparing mastectomy (E-NSM) is a minimal access breast surgery that minimizes and hides the scar inconspicuously, thus optimizing aesthetic outcomes and patient satisfaction (1, 2). Moreover, E-NSM has also demonstrated acceptable oncological safety in some studies (3). However, E-NSM has been controversial as a treatment option, mainly because popular working space-building methods such as liposuction and/or skin lifting systems have some drawbacks (4–6). In addition, E-NSM often requires additional instruments and increases interference, operation time, surgical trauma, and medical costs (6, 7). Furthermore, the superficial nature of the breast and the relatively low morbidity of conventional open breast surgery could also be factors (8).

Surgeons at our center have also tried to conduct E-NSM using retractors to raise the pectoralis major muscle, gland, and skin. However, as in some reports, complications are increased due to uneven stress and unclear dissection layers, and the operation time is very long (9, 10). Through the sum of our experience, our team proposed an innovative technique that involves a changed dissection sequence and incorporates air-insufflation for submuscular space and gland dissection; the technique is named “reverse-sequence endoscopic nipple-sparing mastectomy (R-E-NSM).” Our previous studies have demonstrated that R-E-NSM could create sufficient space, improve dissection access, and avoid interference of instruments. For some challenging part dissection areas, such as the inner-lower quadrant, a small accessory incision (HUAXI hole 1) located at the upper-outer quadrant margin of the areola was introduced so that the final operation time was significantly shortened (11, 12). Because no particular instrument is needed and the operation time is short, this technology is widely accepted in China (13), and we even perform R-E-NSM with breast reconstruction surgeries in the 24-hour surgery center (14–17). We have also used this technology to perform breast reconstruction with endoscopic harvesting of the latissimus dorsi flap (18, 19). Up to now, we have considered R-E-NSM to address the drawbacks of conventional E-NSM (C-E-NSM) and expect it to become a standard surgical procedure. To demonstrate the superiority of the R-E-NSM technique, in this retrospective analysis study, we compared the efficiency, oncological safety, surgical safety, and cosmetic results of patients who underwent C-E-NSM with those of patients who underwent R-E-NSM, followed in each case by subpectoral breast reconstruction (SBR).

This study presents a groundbreaking comparison of two breast cancer surgical procedures, C-E-NSM with SBR and innovation technique R-E-NSM with SBR, in terms of efficiency, safety, and economic results at the first time. The results showed that R-E-NSM outperformed C-E-NSM regarding operation time, anesthesia time, and cost. Moreover, it improved patient satisfaction with the appearance of their scars and revealed a decreasing trend in the incidence of complications. These findings confirm that R-E-NSM is a highly efficient and recommended new surgical procedure that breaks conventional methods. Therefore, R-E-NSM is a promising new surgical procedure that has the potential to revolutionize breast cancer surgery. Given its further development, R-E-NSM is now suitable for a broader range of operations, including subpectoral dual-plane BR, PBR, latissimus dorsi (LD) flap reconstruction, and gynecomastia mastectomy (15, 23, 24).

The operation time was reduced by approximately 2 hours in the R-E-NSM group, and the medical cost and anesthesia time were also reduced compared to C-E-NSM. C-E-NSM increases the difficulty of optimal exposure, such as lifting the pectoralis major muscles, glands, and skin. You cannot have your cake and eat it, too. When the skin-lifting method is chosen, the glands and pectoralis major muscle need to be raised with a retractor and some specific equipment, resulting in poor exposure and difficult dissection of the deep layer. When the air-insufflation method is chosen, using CO₂ exposure is beneficial, but lifting the pectoralis major muscle and the gland with this method is difficult. Therefore, the process of C-E-NSM with SBR will take longer, approximately 5 hours (10, 25).

In contrast, R-E-NSM can resolve the above issue and reduce the operation time using a reverse dissection sequence and CO₂ insufflation. Now you can have your cake and eat it too. With CO₂ insufflation, the field of vision is clearly exposed, and with CO₂ simultaneously just as a universal retractor, the pectoralis major muscle, gland, and skin are lifted easily. An accessory incision (HUAXI hole 1) can also be combined with R-E-NSM to dissect the inner-lower part of the superficial layers of the superficial fascia and prevent equipment interference. The follow-up time was also the reason for the operation time decrease by univariate analyses. We know that the follow-up time reflects the learning curve. As time passes, the surgeon becomes more proficient and experienced. Currently, we only need 60-90 minutes for R-E-NSM with SBR and approximately 60-75 minutes for R-E-NSM with PBR.

Regarding cosmetic outcomes, the SCAR-Q appearance scale is used to evaluate patient satisfaction after developing a surgical scar. Higher scores indicate a better cosmetic outcome. In the R-E-NSM group, the SCAR-Q score was higher, and it was speculated that the reason was that scarring would be more subtle and concealed under the axillary area. There is an axillary incision with a length of approximately 50 mm, combined with a “HUAXI hole 1”, which has a size of 2 mm. Scarring around the breasts is barely noticeable when patients stand erect and hang their arms naturally. From C-E-NSM (10, 26), the incision was mainly placed on the lateral upper side of the breast. Because of a gasless technique and retractor, the incision cannot be close to the top of the axilla. The incision was extended to 5-8 cm to remove the mammary gland and axillary tissue. As a result, scars cannot be concealed completely. The Harris score and Ueda score were more associated with the appearance of breasts which are reported by patients and doctors, respectively. Because the operation method for all patients was subpectoral implant-based breast reconstruction, there was no significant difference in the appearance of the breasts. However, we can also notice a trend from the result that the cosmetic outcomes with R-E-NSM and SBR were better than those with C-E-NSM and SBR.

This study also showed a downward trend of complications in R-E-NSM. Follow-up time was the only independent factor of any surgical complications after multivariate analysis. Therefore, the decreasing trend of complications is not caused by different surgical methods but due to the shorter follow-up time of R-E-NSM and the improvement of surgical proficiency. However, the current complication rate is 7.6% in the R-E-NSM group; with the progress of surgical skill proficiency, the incidence of complications in the R-E-NSM group may be further reduced. Following E-NSM, flap necrosis and NAC necrosis are common complications. However, in this study, there were reports of no cases of flap necrosis in R-E-NSM, and necrosis of the NAC in the R-E-NSM group was lower than that in the C-E-NSM group (1.3% vs. 3.8%), as reported in other studies and even lower than other studies (27–30). Tissue necrosis is associated with damage to blood vessels and enlarged incisions during the operation, and periareolar incisions were identified as predictors of NAC necrosis (29, 31). However, in the R-E-NSM group, gas can evenly expand tissue and expose it well, reducing the damage to surrounding tissues and blood vessels and combining minimal peri-areola accessory incision (HUAXI hole 1), thereby decreasing necrosis complications. Furthermore, a long operation time is a risk factor for surgery site infection (SSI) (32, 33), so reducing the operation time could reduce the probability of SSI. All of the above are reasons for the trend of decreased complication rate after R-E-NSM compared with C-E-NSM.

Oncological safety is a major concern in the treatment of breast cancer. The endoscopic procedures in this study followed the same steps and principles as conventional nipple-sparing mastectomy (C-NSM). Therefore, we speculate that the oncological results of the two techniques may be similar (34). By a median follow-up time of 35 months, the locoregional recurrence rate was 3.8%, the distant metastasis rate was 7.7%, and no patients in the C-E-NSM group experienced mortality. By a median follow-up time of 25 months, there was no report of local recurrence or distant metastasis from patients in the R-E-NSM group. The two-year DFS rate was 96.2% in the C-E-NSM group and 100% in the R-E-NSM group, which is consistent with several studies of C-NSM (35, 36). However, the rate of local recurrence within two years in the R-E-NSM group was lower than that in the C-E-NSM group, although there was no significant difference. In addition to the small sample size due to accidental factors, it has been suggested that insufficient exposure of the retractor, uneven resection, and residual tumor may contribute to the risk of local recurrence in C-E-NSM. The R-E-NSM dissection is even and ranges wider, making it a potentially safer procedure. These results indicate that the oncologic safety of R-E-NSM is acceptable, though the recurrence and survival outcomes are still pending.

R-E-NSM significantly reduced operation time, anesthesia time, and medical cost and showed a downward trend of complications. In particular, patients and doctors in China widely accept R-E-NSM with subpectoral dual-plane BR and PBR to reduce trauma, shorten surgical time, and expand the indication population. These even make R-E-NSM with implant-based breast reconstruction has been successfully performed in the 24-hour surgical center of our hospital. Nevertheless, as a retrospective study, the investigation involved a limited number of cases and was based on the expertise of a single physician and center, resulting in a bias in patient selection, insufficient representation of the general population, and insufficient samples. It is recommended that further prospective cohort studies or randomized controlled trials be conducted.

In summary, R-E-NSM improves cosmetic outcomes and efficiency of C-E-NSM, reduces medical costs, and has a trend of lower surgical complications while maintaining the safety of oncology. It is a safe and feasible option for oncological procedures that deserves to be promoted and widely adopted in practice.

The original contributions presented in the study are included in the article/ Supplementary Material , further inquiries can be directed to the corresponding author.

The study was approved by the Biomedical Ethics Committee of West China Hospital, Sichuan University (No. 2022-570). An exemption from the requirement for informed consent was granted due to the use of retrospective data.

KC: Writing – original draft, Data curation, Formal analysis, Methodology, Writing – review & editing. YX: Data curation, Writing – review & editing. FL: Data curation, Formal analysis, Supervision, Writing – review & editing. MQ: Data curation, Writing – review & editing. HY: Data curation, Writing – review & editing. QZ: Data curation, Writing – review & editing. HD: Data curation, Writing – review & editing. ZD: Supervision, Writing – review & editing, Project administration.