Abdul Kasem

The Oncological Safety of Nipple-Sparing Mastectomy: A Systematic Review of the Literature with a Pooled Analysis of 12,358 Procedures

Nipple-sparing mastectomy (NSM) is increasingly popular as a procedure for the treatment of breast cancer and as a prophylactic procedure for those at high risk of developing the disease. However, it remains a controversial option due to questions regarding its oncological safety and concerns regarding locoregional recurrence. This systematic review with a pooled analysis examines the current literature regarding NSM, including locoregional recurrence and complication rates. Systematic electronic searches were conducted using the PubMed database and the Ovid database for studies reporting the indications for NSM and the subsequent outcomes. Studies between January 1970 and January 2015 (inclusive) were analysed if they met the inclusion criteria. Pooled descriptive statistics were performed. Seventy-three studies that met the inclusion criteria were included in the analysis, yielding 12,358 procedures. After a mean follow up of 38 months (range, 7.4–156 months), the overall pooled locoregional recurrence rate was 2.38%, the overall complication rate was 22.3%, and the overall incidence of nipple necrosis, either partial or total, was 5.9%. Significant heterogeneity was found among the published studies and patient selection was affected by tumour characteristics. We concluded that NSM appears to be an oncologically safe option for appropriately selected patients, with low rates of locoregional recurrence. For NSM to be performed, tumours should be peripherally located, smaller than 5 cm in diameter, located more than 2 cm away from the nipple margin, and human epidermal growth factor 2-negative. A separate histopathological examination of the subareolar tissue and exclusion of malignancy at this site is essential for safe oncological practice. Long-term follow-up studies and prospective cohort studies are required in order to determine the best reconstructive methods.

Breast Lipofilling: A Review of Current Practice

Lipofilling is a reconstructive and aesthetic technique that has recently grown in popularity and is increasingly being used in breast surgery. Previous concerns had been raised regarding its safety when used for remodelling and reconstruction of the breast; however, these concerns have since been dismissed. Over the subsequent two decades, little evidence has been found to support these early theoretical concerns, and growing numbers of proponents of the procedure are confident in its safety. Many developments and refinements in the technique have taken place in recent years, and several studies have been published regarding the safety of lipofilling in the breast. We reviewed the current literature regarding the use of different lipofilling techniques as well as the current evidence regarding the oncological safety of the procedure in patients seeking aesthetic breast enhancement and in patients requiring reconstruction after treatment for breast cancer.

Evolving role of skin sparing mastectomy

Skin sparing mastectomy (SSM) can facilitate immediate breast reconstruction and is associated with an excellent aesthetic result. The procedure is safe in selected cases; including invasive tumours < 5 cm, multi-centric tumours, ductal carcinoma in situ and for risk-reduction surgery. Inflammatory breast cancers and tumours with extensive involvement of the skin represent contra-indications to SSM due to an unacceptable risk of local recurrence. Prior breast irradiation or the need for post-mastectomy radiotherapy do not preclude SSM, however the aesthetic outcome may be compromised. Preservation of the nipple areola complex is safe for peripherally located node negative tumours. An intraoperative frozen section protocol for the retro-areolar tissue should be considered in these cases. The advent of acellular tissue matrix systems has enhanced the scope of implant-based immediate reconstruction following SSM. Cell-assisted fat transfer is emerging as a promising technique to optimise the aesthetic outcome.

mRNA expression of DOK1-6 in human breast cancer

AIM To examine the expression of downstream of tyrosine kinase (DOK)1-6 genes in normal and breast cancer tissue and correlated this with several clinico-pathological and prognostic factors. METHODS DOK1-6 mRNA extraction and reverse transcription were performed on fresh frozen breast cancer tissue samples (n = 112) and normal background breast tissue (n = 31). Tissues were collected between 1991 and 1996 at two centres and all patients underwent mastectomy and ipsilateral axillary node dissection. All tissues were randomly numbered and the details were only made known after all analyses were completed. Transcript levels of expression were determined using real-time polymerase chain reaction and analyzed against TNM stage, tumour grade and clinical outcome over a 10-year follow-up period. RESULTS DOK-2 and DOK-6 expression decreased with increasing TNM stage. DOK-6 expression decreased with increasing Nottingham Prognostic Index (NPI) [NPI-1 vs NPI-3 (mean copy number 15.4 vs 0.22, 95%CI: 2.7-27.6, P = 0.018) and NPI-2 vs NPI-3 (mean copy number 7.6 vs 0.22, 95%CI: 0.1-14.6, P = 0.048)]. After a median follow up period of 10 years, higher levels of DOK-2 expression were found among patients who remained disease-free compared to those who developed local or distant recurrence (mean copy number 3.94 vs 0.0000096, 95%CI: 1.0-6.85, P = 0.0091), and distant recurrence (mean copy number 3.94 vs 0.0025, 95%CI: 1.0-6.84, P = 0.0092). Patients who remained disease-free had higher levels of DOK-6 expression compared to those who died from breast cancer. CONCLUSION Decreasing expression levels of DOK-2 and DOK-6 with increased breast tumour progression supports the notion that DOK-2 and DOK-6 behave as tumour suppressors in human breast cancer.

Can Complete Axillary Node Dissection Be Safely Omitted in Patients with Early Breast Cancer When the Sentinel Node Biopsy Is Positive for Malignancy? An Update for Clinical Practice

The sentinel lymph node biopsy (SLNB) has become the new standard-of-care for patients with clinically node-negative invasive breast cancer. The focused examination of fewer lymph nodes in addition to improvements in histopathological and molecular analysis have increased the rate at which micrometastases and isolated tumor cells are identified. We reviewed the literature and summarized the evidence regarding the need for complete axillary lymph node dissection (ALND) following the finding of a positive sentinel node biopsy through the identification of the most important outcomes and evaluation of quality of evidence. The article focuses on the safe omission of complete ALND when the axillary lymph nodes contain macrometastases and provides an overview of the topic primarily based on level 1 evidence derived from randomized clinical trials with a critical appraisal of the ACOSOG Z0011 trial.

The Impact of EndoPredict Clinical Score on Chemotherapy Recommendations in Women with Invasive ER+/HER2−Breast Cancer Stratified as Having Moderate or Poor Prognosis by Nottingham Prognostic Index

Background: The Nottingham Prognostic Index (NPI) was developed using tumour pathological features to guide decisions regarding adjuvant therapy in breast cancer. Recent breakthroughs in molecular biology aided development of genomic assays such as EndoPredict, which have been shown to provide excellent prognostic information. The current study investigated the impact of EndoPredict Clinical (EPClin), a composite of clinicopathological data and EndoPredict score, on chemotherapy recommendations based on NPI. Patients and Methods: A total of 120 patients with oestrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer who were candidates for post-operative adjuvant chemotherapy at a single tertiary centre were included. Both NPI and EPClin were applied to all patients. NPI differentiated patients into groups with excellent/good prognosis (N=41; NPI≤3.4) or moderate/poor prognosis (N=79; NPI >3.4). The latter were considered for adjuvant chemotherapy. Results: There was discordance in results of 31% of cases; 35% of the patients/candidates for adjuvant chemotherapy according to NPI were reclassified as being at low risk of recurrence by EPClin. Conclusion: Genomic profiling using EPClin reduces the potential need for adjuvant chemotherapy in women with ER+/HER2− breast cancer who are candidates for chemotherapy according to the NPI.

Porcine acellular dermis-based breast reconstruction: complications and outcomes following adjuvant radiotherapy

Sir, We read the study by Ng and colleagues [1] with great interest. In their study, the authors report on the use of an acellular dermal matrix (ADM, StratticeTM, LifeCell, NJ, USA) in the setting of breast reconstruction and radiotherapy treatment. In their study, Ng and colleagues describe an overall complication rate of 32 % with no significant difference between those treated with radiotherapy before surgery and those treated postoperatively. They therefore conclude that implant-based reconstruction using StratticeTM should not be an absolute contraindication in preor post-radiotherapy patients, but that the increased risks are emphasised to patients in order to better manage patient expectations if complications arise. With up to one third of women opting for mastectomy [2], the use of ADMs in breast reconstruction is becoming increasingly popular, being described as the most significant innovation impacting prosthetic breast reconstruction in recent years [3]. We recently undertook a similar study, looking at the use of a bovine-derived ADM, SurgiMendTM (TEI Biosciences, MA, USA), in a prospective case series of 118 patients undergoing 164 skin sparing mastectomy and immediate reconstruction procedures. Thirty-two patients (27 %) in our series underwent radiotherapy, of whom 27 received postmastectomy radiotherapy and 5 received it prior to surgery. Fifty-two percent of the patients received chemotherapy. Despite this relatively high uptake rate of chemotherapy and radiotherapy, we found a relatively low complication rate. At a mean follow-up of 21 months, the explantation rate was 1.2 %, and 4 % of patients developed wound complications. This included one case of partial wound dehiscence requiring surgical debridement and implant replacement in a patient who had undergone both postmastectomy radiotherapy and chemotherapy. Another patient who also received radiotherapy prior to surgery developed capsular contracture after 2 years which required capsulotomy and fat transfer. Those who lost their implants were undergoing adjuvent chemotherapy. We also found that there was high patient satisfaction with the outcome of the procedure (9 out of 10). We therefore agree with the conclusions reached by Ng and colleagues: ADM-assisted breast reconstruction should not be an absolute contraindication in patients receiving radiotherapy. The difference between results may be explained by differences in surgical technique or the different ADMs used in each of the studies, as follow-up times were similar. Furthermore, other factors have been reported to affect complication rate, such as body mass and comorbidity status; therefore, patient selection may also play a role. As Ng rightly point out, it is important to ensure that patients have adequate * Kefah Mokbel kefahmokbel@hotmail.com

Abstract P2-13-04: Clinical outcome and patient satisfaction with the use of bovine-derived acellular dermal matrix (SurgiMendTM) in implant-based immediate reconstruction following skin sparing mastectomy: A prospective observational study

The advent of acellular dermal matrix devices (ADMs) has facilitated immediate breast reconstruction (IBR) with mammary implants following skin sparing mastectomy (SSM) for breast cancer treatment or risk reduction. This is a prospective observational single institution study of 118 consecutive patients undergoing a total of 164 SSM and IBR procedures using an implant and bovine-derived ADM (SurgiMend) for breast cancer or risk reduction purposes during 2012-2014. The primary endpoint was the explantation rate and secondary endpoints included patient quality of life, patient satisfaction, objective assessment of aesthetic outcome, surgical complications, recurrence and mortality. The mean age of the patients was 50.1 years (median age of 48, range of 27-78). Median follow up time was 21 months (mean of 21.4 months, range of 2-40 months). 46 patients had a bilateral SSM and IBR, 5 of whom had bilateral breast cancer and 3 for risk reduction due to a significant genetic mutation. The remaining 37 patients had unilateral breast cancer and a contralateral risk reducing mastectomy. 27 (37.5%) of the 72 patients who had unilateral SSM underwent contralateral adjustment procedures to optimise symmetry, including 9 augmentation mammoplasty, 12 mastopexy and 4 reduction mammaplasty procedures and 2 combined augmentation-mastopexies. 61 patients (51.7%) received chemotherapy, 5 of whom had primary systemic therapy prior to surgery. 32 (27.1%) patients received radiotherapy (10 patients had prior radiotherapy and 22 patients had post mastectomy radiation: PMR). Those with ER positive disease received hormonal therapy. Those with Her2 positivity received Herceptin +/- Pertuzumab. Over the study period, 2 implants had to be removed resulting in an explantation rate of 1.2%. Overall, wound complications were observed in 6 (3.7%) cases. There were 2 cases of local recurrence (1.7%), one distant recurrence (0.8%) and one patient died of metastatic breast cancer (0.8%). Overall survival was 99.2% and locoregional disease free survival (LRFS) was 98.3%. One patient (0.8%) developed a mild inflammatory reaction secondary to the underlying mesh. Wound complications were observed in 3 other patients (2 haematomas and wound dehiscence/persistent seroma requiring implant replacement). Patient satisfaction with the procedure was very high. The mean Breast Q Score was 85 and mean overall patient satisfaction was 9 out of a possible 10. The mean objective assessment score was 8.9 out of a possible 10 and the mean subjective capsular contracture severity score was 2.9 out of 10. In patients undergoing reoperations, the incorporation rate of the mesh was found to be very high almost approaching 95%. SurgiMendTM is an effective adjunct to IBR using implants following SSM for breast cancer or risk reduction, with a very low rate of implant loss and a high level of patient satisfaction. Furthermore, this ADM seems to incorporate readily and is associated with a very low incidence of inflammatory reactions. Neither prior radiotherapy nor PMR radiation represents a contraindication to its use. Citation Format: Wazir U, Kasem A, Headon H, Choy C, Manson A, Heeney J, Mead O, Mokbel K. Clinical outcome and patient satisfaction with the use of bovine-derived acellular dermal matrix (SurgiMendTM) in implant-based immediate reconstruction following skin sparing mastectomy: A prospective observational study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-13-04.

Abstract P2-12-11: Does postmastectomy radiotherapy improve survival in patients with 1-3 positive axillary lymph nodes? A systematic review and meta-analysis of the current literature

In breast cancer with more than four positive axillary lymph nodes, it is common practice to deliver radiotherapy to the affected site following a mastectomy. However, less is known about the benefit s this might offer in women with 1-3 positive lymph nodes. In order to assess whether postmastectomy radiotherapy has any benefit in these women, a meta-analysis was performed to assess whether postmastectomy radiotherapy improved overall survival or reduced locoregional recurrence in this group of women. It was found that postmastectomy radiotherapy significantly reduced the risk of locoregional recurrence, with a relative risk ratio of 0.3 (95% confidence interval 0.23-0.38), and resulted in a small benefit in overall survival, with a relative risk ratio of 1.03 (95% confidence interval 1.00-1.07). Therefore, in women with 1-3 positive lymph nodes, postmastectomy radiotherapy reduces the risk of locoregional recurrence and is associated with a small benefit in overall survival, so should be recommended within this group after careful multidisciplinary discussion. Citation Format: Kasem A, Headon H, Mokbel K. Does postmastectomy radiotherapy improve survival in patients with 1-3 positive axillary lymph nodes? A systematic review and meta-analysis of the current literature. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-12-11.

Abstract P2-13-08: Breast lipofilling: A systematic review of current practice and oncological safety

Background: Lipofilling is a reconstructive and aesthetic technique that has recently grown in popularity and is increasingly being used in breast surgery. Concerns had been raised regarding its safety when used for remodelling and reconstruction of the breast. Methods: We reviewed the current literature by systematically searching PubMed and Google Scholar databases regarding the current evidence regarding the oncological safety of the procedure in patients seeking aesthetic breast enhancement and in patients requiring oncoplastic reconstruction. Results: Among the 864 patients included in the currently available studies on breast cancer patients who underwent lipofilling, only 14 (1.6%) recurrences were identified. However, evidence has emerged suggestive that the use of lipofilling in the background of ductal carcinoma in situ (DCIS) may be associated with an increased risk of neoplasia. Conclusions: Over the subsequent two decades, little evidence has been found to support these early theoretical concerns, and growing numbers of proponents of the procedure are confident in its safety. Further study is required to better delineate the effect of lipofilling on DCIS. Citation Format: Wazir U, Kasem A, Headon H, Mokbel K. Breast lipofilling: A systematic review of current practice and oncological safety. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-13-08.