DISCUSSION:
The excision volume required to safely perform BCS can be reduced by neoadjuvant therapy (12). Regardless of the administration of neoadjuvant therapy, poor cosmetic outcomes are obtained in cases where large excisions are required to perform BCS (13). Furthermore, surgical margin positivity and re-excision rates are quite high after BCS (14). Oncoplastic surgery allows larger volume excision without impairing cosmetic outcomes and reduces re-excision rates (15). Primary tumor size decreases after neoadjuvant therapy. In such cases, the success of the treatment in terms of local control depends on the accurate tumor localization. It is aimed to excise the accurate area at sufficient volume after NAC by marking the tumor in the pre-NAC period, determining localization by means of seeds containing radioactive material, and applying intraoperative USG. However, pre-NAC marking cannot adequately guide the clinician for tumors showing non-concentric shrinkage patterns. Intraoperative localization techniques may remain inadequate in this regard (16,17). In tumors that shrink into fragments, the residual radiological disease should be evaluated and, if necessary, marked after NAC. At this point, the question of whether unplanned surgery can provide safe oncological results should arise. The answer to this question has been investigated in patients who primarily underwent BCS. In the National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-18 trial, the local recurrence rate was reported to be 15.9% in unplanned surgery and 9.3% in planned surgery. The difference was statistically significant (2). The European Organization for Research and Treatment of Cancer (EORTC) 10920 trial reported higher local recurrence rates with unplanned surgery (3). In a study by Shin et al. (10) involving patients with stage III breast cancer, the results of planned BCS, unplanned BCS, and mastectomy were compared in patients with a tumor size of less than 4 cm after NAC. The authors reported that five-year LRFS was 90.9% in patients undergoing unplanned surgery, while this rate was 96.3% in patients undergoing mastectomy (10). In the series published by Fitzal et al. (9), BCS was performed in 110 of 221 patients scheduled for mastectomy before NAC. While unplanned surgery was observed to have no disadvantage in terms of local control in patients with a good response to NAC, local recurrence rates were found to be higher in the unplanned surgery arm in patients with an insufficient response. The technique used in all these studies was BCS, but the neoadjuvant therapy criteria were not standard. It should be kept in mind that the number of patients receiving neoadjuvant therapy and the rate of responses to treatment have increased at the present time. Furthermore, advanced imaging techniques may increase the possibility of localization after NAC.
More than 20% of breast volume and a significant amount of breast skin is excised in Level II techniques and simultaneous reconstruction is performed with more complicated and sophisticated glandular flap methods. On the other hand, less than 20% of the total breast volume is excised and the volume excision is limited in Level I techniques. Youssef et al. (18) presented post-NAC OPS results in a series of 70 patients. In this series where tumor marking was not performed before NAC, the rate of IBTR was reported as 4.2% and Level I OPS techniques were applied to %57 of the patients. The mean surgical margin distance was found to be wider in patients for whom Level II techniques were applied (25 mm vs. 10 mm). In the present series, Level II OPS techniques were applied to all of our patients. Although not statistically significant, the mean surgical margin distance was found to be wider in the unplanned surgery group (18 mm vs. 14 mm). Surgeons likely tend to excise more tissue to provide a firm surgical margin in unmarked patients. In a study by Chauhan et al. (19), patients who underwent OPS and BCS after NAC were compared. In the whole series, reduction in the form of fragmentation was detected at a rate of 44% and the tumor bed was marked with a clip in all patients before NAC. Skin tattooing was performed, if necessary, to promote localization after NAC. While the mean specimen volume and mean surgical margin distance were larger in patients undergoing OPS, the ratio of involved margin and IBTR was lower. In the literature, IBTR rates in patients undergoing planned OPS after NAC were observed to range from 6% to 10% (20,21). A matching case-control study comparing patients who underwent BCS and OPS after NAC was reported from Brazil. Planned surgery was applied to all patients. In this series, the majority of which consisted of patients with T3 tumors, the volume of the excised specimen and mean surgical margin distance were larger in the OPS group. During an average follow-up of 67 months, the rate of IBTR was found to be 10.2%. In this series, Level I OPS techniques were applied to nearly half of the patients in the OPS group. Longer follow-up time and non-standardized surgical techniques may explain the high local recurrence rates in this series (22). Similar results were reported by Mazouni et al. (23) from France. Pre-NAC primary tumor marking was not standard in this series. Post-NAC tumor size and specimen volume were found to be larger in patients undergoing OPS. The re-excision rate was reported to be 2% in patients undergoing OPS whereas it was 9% in patients undergoing BCS. The requirement for mastectomy was 24% vs 18%, respectively, in patients who underwent BCS and OPS (23). In our series, there were no patients who underwent conventional BCS. Although re-excision rates in patients who underwent OPS were found to be higher in our series compared to the said study, the requirement for mastectomy was found to be lower in patients undergoing planned and unplanned OPS. Five-year 5% local recurrence rates, on the other hand, were found to be similar to our series.
In the present series, mastectomy was performed after systemic treatment in the presence of extensive skin involvement, skin edema, chest wall involvement, and diffuse microcalcification. Performing mastectomy in patients with any of these conditions is currently considered as standard treatment. However, we were able to successfully perform OPS after systemic therapy in our patients in the presence of minimal edema and skin shrinkage around the tumor. This feature makes the present study different from others.
Tumor shrinkage after NAC in locally advanced breast cancer may occur in three ways. First, a complete clinical response can be seen in the tumor. In this case, pre-NAC tumor marking makes the planning of surgical treatment easier; however, the previous tumor bed can be still displayed in post-NAC radiological examinations. Surgery can be planned by taking this area as the center. Secondly, tumor sizes can be reduced and a concentric response can be achieved, and no tumor nodules may be seen in the periphery of the tumor. In this case, surgery can be planned by taking residual tumor as a basis in the post-NAC period. The third shrinkage pattern is called the mosaic pattern, where the tumor shrinks by breaking into small pieces. In this case, pre-NAC marking of the tumor is not sufficient to perform the surgery safely. The margins of the nodules located in the periphery of the tumor should be known or marked in the post-NAC period. Secondary surgical intervention is mandatory for patients with involved resection margins, resulting in poor cosmetic outcomes or loss of the breast. It further means increased costs and psychological stress for the patient. The marking of the tumor in both pre- and post-NAC periods is likely to be more meaningful. Figures 2 and 3 present images related to OPS performed with post-NAC wire localization on the patient with a tumor that shrank concentrically with NAC.
This study has shown that BCS can be applied using level II OPS techniques with the post-NAC radiological examination and marking even if primary tumor marking is not done in the pre-NAC period. The rates of re-excision and mastectomy requirement similar to the patients undergoing planned OPS and mastectomy have been obtained in those undergoing post-NAC unplanned OPS. Furthermore, long-term local control rates are similar. The absence of pre-NAC primary tumor marking is not a condition that necessarily requires a mastectomy. Moreover, localized skin involvement and localized edema should not be considered a contraindication for OPS.
A cknowledgements: None
Statement of Ethics : This study was conducted with the permission of the local ethics committee. Ethics committee approval number: AOH/125/12
InformedConsent: Written informed consent was obtained from patients who participated in this study.