Is Autologous Fat Grafting an Oncologically Safe Procedure following Breast Conserving Surgery for Breast Cancer? A Comprehensive Review.

BACKGROUND: Autologous fat grafting (AFG) is a recognized surgical procedure to correct deformities following breast conservation surgery (BCS) for breast cancer. However, there are concerns about the oncological safety of this technique. In this study we have reviewed the current literature to assess whether AFG adversely influences the oncological outcome after BCS for breast cancer. METHODS: We have searched the medical literature using the Embase and PubMed search engines from conception until May 2019 to identify all relevant studies of patients who underwent AFG after BCS. Meta-analysis and meta-regression methodologies were used to calculate the overall relative risk (RR) of loco-regional recurrence (LRR) rates for case-control and case series studies (with historical controls) respectively. RESULTS: We have identified 26 eligible studies with a total of 1640 patients who had undergone fat transfer after lumpectomy for breast cancer. The meta-analysis of 11 studies revealed an overall RR for LRR of 0.82 [95% confidence interval (CI):0.14-1.66]. The meta-regression of case series revealed an overall incidence of LRR of 1.85% compared with 2.53% for historical controls. CONCLUSIONS: Our study lends further support to the notion that fat transfer after lumpectomy for breast cancer does not seem to increase the risk of LRR. However further prospective research is required in order to confirm this.

Is it Possible to Predict Non Sentinel Node Positivity on the Basis of mRNA Copy Numbers of CK19 Receptor in Breast Cancer?

AIMS: To determine if there is any correlation between the number of positive non-sentinel lymph nodes (NSLN) and the mRNA copy numbers of cytokeratin 19 receptor on one step nucleic acid amplification (OSNA) in the sentinel lymph node (SLN). METHODS: An 8-year retrospective study of consecutive patients who had primary surgery and sentinel node biopsy for breast cancer from January 2011 to December 2018 was carried out. All these patients had intra-operative analysis of sentinel lymph nodes by OSNA. Patients who had neoadjuvant chemotherapy or neoadjuvant endocrine therapy were excluded. RESULTS: There were 1159 patients with an age range of 24 to 90 years and a mean age of 63 years in this study. A total of 1324 SLNs were analyzed by OSNA. Macrometastasis was found in 120 patients and they underwent axillary lymph node dissection (ALND). A total of 2405 NSLNs were analyzed. Of the patients who had ALND, 51 (43%) patients had negative NSLNs and 69 (57%) had positive NSLNs. The mean mRNA copy numbers respectively for the 2 groups were 853,665 and 609,855. The difference between the means is not statistically significant (P = 0.82). Also the Receiver Operating Characteristic (ROC) Curve of the total CK-19 mRNA copy number for both groups-negative and positive NSLN were almost identical (Figure 3) indicating mRNA copy numbers cannot be used to discriminate between positive and negative non-sentinel lymph nodes. CONCLUSION: It is clear from our study that in patients who have ALND due to macromets on OSNA, there is no correlation between the total tumor load as represented by mRNA copy numbers and the likelihood of positive non-sentinel lymph nodes. We therefore cannot rely solely on the mRNA copy numbers to decide on ALND.

Novel wire-free techniques for localization of impalpable breast lesions-A review of current options.

Localization methods for breast lesions including cancers have changed and advanced since their inception. Currently, the most widely used technique in the United Kingdom is the image-guided hook wire localizer developed in the 1970s. It remains as the gold standard for localization of impalpable breast tumors. Besides its advantages, there are some disadvantages associated with this technique. In recent years, novel wire-free techniques (eg, Magseed® , SCOUT® , and LOCalizer™) have been developed to not only localize impalpable breast lesions but also negate the disadvantages of wire localization. This article reviews the variety of techniques from their origins to the most recent advancements that are used to localize breast lesions. The future is heading toward non-wire technology and wire localization may then be reserved for special cases.

Locoregional therapy of the primary tumour in de novo stage IV breast cancer in 216 066 patients: A meta-analysis.

Patients presenting with de novo stage IV metastatic breast cancer have a complex disease which is normally treated with palliative intent and systemic therapy. However, there is mounting evidence that resection of the primary tumour and/or localised radiotherapy (locoregional therapy; LRT) could be associated with overall survival improvements. We aimed to conduct a meta-analysis to inform decision making. Using the PubMed, Cochrane and Ovid SP databases, a literature review and meta-analysis were conducted to assess the effect of LRT on overall survival. Studies were analysed for the impact of LRT on survival. All forms of LRT resulted in a significant 31.8% reduction in mortality (N = 42; HR = 0.6823 (95% CI 0.6365; 0.7314)). Surgical resection resulted in a significant 36.2% reduction in mortality (N = 37; HR = 0.6379 (95% CI 0.5974; 0.6811)). The prospective trials reported a 19.23% reduction in mortality which was not statistically significant (N = 3, HR = 0.8077 (95% CI 0.5704; 1.1438). 216 066 patients were included. This is the largest meta-analysis regarding this question to date. Our meta-analysis shows that LRT of the primary tumour seems to improve overall survival in de novo stage IV disease. Therefore, this therapeutic option should be considered in selected patients after a careful multidisciplinary discussion.

Is oncoplastic breast conserving surgery oncologically safe? A meta-analysis of 18,103 patients.

BACKGROUND: Oncoplastic Breast Conserving Surgery (OBCS) allows adequate resection margins of tumours unsuitable for standard breast conserving surgery (SBCS) whilst allowing for better cosmesis and reduced morbidity when compared to mastectomy. However, there is limited evidence on its oncological safety. METHODS: This study aims to compare oncological safety of OBCS with SBCS and mastectomy by examining the relative risk of cancer recurrence and re-operation rates through meta-analysis. RESULTS: 18 studies met the search criteria including 18,103 patients. The primary outcome measure (recurrence) was not significantly different between OBCS and SBCS or mastectomy (RR 0.861; 95% CI 0.640-1.160; p = 0.296). The secondary outcome measure (re-operation) initially achieved significance in favour of OBCS (RR 0.64; 95% CI 0.46-0.89; p = 0.01). However, after adjustment for publication bias this was attenuated to insignificance between the two study groups (RR 0.86; 95% CI 0.56-1.31; p = 0.44). CONCLUSIONS: For both cancer recurrence and re-operation rate, there was no significant difference between OBCS and traditional techniques. OBCS is of comparable oncological safety to more established surgical procedures and a useful option in suitable patients.

A Study of the Relation Between Mastectomy Specimen Weight and Volume With Implant Size in Oncoplastic Reconstruction.

BACKGROUND: There is no general consensus regarding the best and most accurate method for assessing the size of implant required for achieving the best symmetry in oncoplastic reconstruction. MATERIALS AND METHODS: Breast weight, volume and size of implant were recorded prospectively on patients undergoing immediate reconstruction over a 3-year period. Cases with specimen size greater than 2,000 g were excluded. The primary endpoint was size of implant used in relation to specimen weight and volume. Secondary endpoints were the influence of age and histology on specimen weight, volume and breast density. RESULTS: A total of 278 mastectomies were performed. Correlation of implant size with volume was marginally stronger than that with weight (r=81%, p<0.001 vs. r=78.9%, p<0.001 respectively). Women aged 50 years and above had lower breast weight for the same breast volume than women under 50 years. The difference was merely 4%, but was statistically significant (p=0.001). Histology had no statistically significant influence on breast density. CONCLUSION: Specimen weight and volume were found to be closely correlated. Weight can be measured more accurately and easily with reproducible readings compared to volume.

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.

Do online prognostication tools represent a valid alternative to genomic profiling in the context of adjuvant treatment of early breast cancer? A systematic review of the literature.

INTRODUCTION: Decision-making regarding adjuvant chemotherapy has been based on clinical and pathological features. However, such decisions are seldom consistent. Web-based predictive models have been developed using data from cancer registries to help determine the need for adjuvant therapy. More recently, with the recognition of the heterogenous nature of breast cancer, genomic assays have been developed to aid in the therapeutic decision-making. METHODS: We have carried out a comprehensive literature review regarding online prognostication tools and genomic assays to assess whether online tools could be used as valid alternatives to genomic profiling in decision-making regarding adjuvant therapy in early breast cancer. RESULTS AND CONCLUSIONS: Breast cancer has been recently recognized as a heterogenous disease based on variations in molecular characteristics. Online tools are valuable in guiding adjuvant treatment, especially in resource constrained countries. However, in the era of personalized therapy, molecular profiling appears to be superior in predicting clinical outcome and guiding therapy.

Nipple-sparing mastectomy using a hemi-periareolar incision with or without minimal medial-lateral extensions; clinical outcome and patient satisfaction: A single centre prospective observational study.

BACKGROUND: Nipple-sparing mastectomy (NSM) is becoming a viable oncoplastic option. There is debate regarding the best approach that balances oncological safety with aesthetics. In this study, we describe an approach involving a hemi-periareolar incision and evaluate its safety and outcomes. METHODS: Patients treated at single center between 2012 and 2015 were observed prospectively. After a histologically negative subareolar biopsy, immediate reconstruction with implant and acellular dermal matrix was performed after NSM. Primary end points were wound complications and explantation. Secondary end points included local recurrence, quality of life, patient satisfaction, and esthetic outcome. RESULTS: Sixty-three patients were included with 92 procedures. Twenty-seven percent received chemotherapy and 12.7% received radiotherapy. Mean follow-up was 27.6 months. There were only 2 wound complications, and no recurrences. Mean outcome scores were promising (Breast Q = 88%, subjective esthetic = 9.2, objective esthetic = 9.3, hardening = 2.6). CONCLUSIONS: NSM via a hemi-periareolar incision is oncologically safe with a low-complication rate and high patients' satisfaction.

Is sentinel lymph node biopsy indicated in patients with a diagnosis of ductal carcinoma in situ? A systematic literature review and meta-analysis.

BACKGROUND: Recent discussion has suggested that some cases of ductal carcinoma in situ (DCIS) with high risk of invasive disease may require sentinel lymph node biopsy (SLNB). METHODS: Systematic literature review identified 48 studies (9,803 DCIS patients who underwent SLNB). Separate analyses for patients diagnosed preoperatively by core sampling and patients diagnosed postoperatively by specimen pathology were conducted to determine the percentage of patients with axillary nodal involvement. Patient factors were analyzed for associations with risk of nodal involvement. RESULTS: The mean percentage of positive SLNBs was higher in the preoperative group (5.95% vs 3.02%; P = .0201). Meta-regression analysis showed a direct association with tumor size (P = .0333) and grade (P = .00839) but not median age nor tumor upstage rate. CONCLUSIONS: The SLNB should be routinely considered in patients with large (>2 cm) high-grade DCIS after a careful multidisciplinary discussion. In the context of breast conserving surgery, the SLNB is not routinely indicated for low- and intermediate-grade DCIS, high-grade DCIS smaller than 2 cm, or pure DCIS diagnosed by definitive surgical excision.

Improvement of survival with postmastectomy radiotherapy in patients with 1-3 positive axillary lymph nodes: A systematic review and meta-analysis of the current literature.

In breast cancer with >4 positive axillary lymph nodes, it is common practice to deliver radiotherapy to the affected site following mastectomy. However, less is known regarding the benefits this may confer on women with 1-3 positive lymph nodes. In this meta-analysis, we aimed to assess whether post-mastectomy radiotherapy (PMRT) was beneficial for such patients. A literature review was conducted using the PubMed and Ovid databases. Selected studies were analysed and data regarding overall survival (OS) and locoregional recurrence (LRR) rates were extracted. Statistical analysis was then conducted in order to develop a combined risk ratio (RR) for both OS and LRR in the setting of PMRT in women with breast cancer with 1-3 positive lymph nodes. PMRT in women with 1-3 positive lymph nodes significantly reduced the risk of LRR, with a RR of 0.3 [95% confidence interval (CI): 0.23-0.38] and also showed a minor benefit in terms of OS (RR=1.03, 95% CI: 1.00-1.07). Therefore, in breast cancer patients with 1-3 positive lymph nodes, PMRT significantly reduced the risk of LRR and was associated with a minor OS benefit. Until the results of ongoing randomised controlled trials are published, PMRT should be recommended in this group of patients following a careful multidisciplinary discussion.

Oncological Safety of Lipofilling in Patients with Breast Cancer: A Meta-analysis and Update on Clinical Practice.

BACKGROUND: Lipofilling is an increasingly popular technique for breast reconstruction following both mastectomy and breast-conserving surgery (BCS). However, concerns remain over its oncological safety and its effect on cancer recurrence. MATERIALS AND METHODS: A systematic literature review and meta-analysis was carried out. Patients who had undergone mastectomy or BCS were investigated separately in order to find out whether the addition of lipofilling had a significant effect on locoregional recurrence rate. RESULTS: Eleven studies were used in the analysis, yielding a total of 2,382 patients. For patients undergoing mastectomy (mean follow-up=36.2 months, range=12-90 months) or BCS (mean follow-up=30.2 months, range=12-60 months), the addition of lipofilling was not found to significantly affect the locoregional recurrence rate. CONCLUSION: This meta-analysis demonstrates that lipofilling is an oncologically safe procedure to be incorporated into breast reconstruction following either mastectomy or BCS for breast cancer. However, a careful oncological follow-up is recommended. In the future, more adequately powered controlled clinical trials are needed in order to fully understand long-term outcomes after lipofilling.

Is sentinel lymph node biopsy a viable alternative to complete axillary dissection following neoadjuvant chemotherapy in women with node-positive breast cancer at diagnosis? An updated meta-analysis involving 3,398 patients.

BACKGROUND: The use of sentinel lymph node biopsy (SLNB) following neoadjuvant chemotherapy (NAC) in patients presenting with clinically positive lymph nodes remains controversial. METHODS: A computer-aided search of the literature regarding SLNB in clinically node-positive breast cancer treated with NAC was carried out to identify the false negative rate (FNR), sentinel lymph node identification rate (IR), and axillary pathological complete response (pCR). RESULTS: Nineteen articles were used in the analysis yielding 3,398 patients. The pooled estimate of the FNR was 13% and that of the IR was 91%. The adjusted pCR rate was 47%. A trend toward significance was observed with only clinical stage N1 (cN1) disease whereby clinical stage N1 was associated with an increased pCR rate when compared to N2 or N3 disease (P = .06). CONCLUSIONS: SLNB after NAC in biopsy-proven node-positive patients results in reasonably acceptable FNR and IR, making it a valid alternative management strategy to axillary dissection. More refined patient selection and optimal techniques can improve the FNR and IR in this patient population.

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.

Clinical outcome and patient satisfaction with the use of bovine-derived acellular dermal matrix (SurgiMend™) in implant based immediate reconstruction following skin sparing mastectomy: A prospective observational study in a single centre.

INTRODUCTION: The advent of acellular dermal matrix devices (ADMs) has enhanced both the scope of implant-based immediate breast reconstruction (IBR) following skin sparing mastectomy (SSM) for the treatment or risk reduction of breast cancer. Currently, there are a wide range of options available for the use of ADMs. METHODS: This is a prospective observational single institution study of 118 consecutive patients undergoing a total of 164 SSM and IBR procedures either for treatment for breast cancer or for risk reduction, between 2012 and 2014. IBR was performed using an implant and bovine-derived ADM (SurgiMend™). Nipple sparing mastectomy (NSM) accounted for 103 procedures. IBR was performed as a single stage procedure in 23% of patients. The primary endpoint of this prospective study was the explantation rate and secondary endpoints included quality of life, patient satisfaction, aesthetic outcome assessed objectively, surgical complications, overall and disease free survival. RESULTS: Forty-six patients (39%) had a bilateral and 72 underwent a unilateral SSM. Of those who underwent a unilateral SSM, 25 had a contralateral adjustment procedure. Out of 164 procedures, 117 (71%) were for the treatment of breast cancer. Sixty-one patients received chemotherapy (52%) and 32 (27%) had radiotherapy. In this study 27 patients underwent post-mastectomy radiotherapy. At a mean follow of 21 months, the explantation rate was 1.2%, 4% (6 patients) developed wound complications. The patient satisfaction with the procedure was found to be very high. The mean Breast Q Score was 85 and the mean overall patient satisfaction rating 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. There were two 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. CONCLUSIONS: SurgiMend™ is an effective adjunct to implant based IBR following SSM. It is associated with a very low rate of implant loss and a high level of patient satisfaction and is associated with a very low incidence of inflammatory reaction. Neither prior radiotherapy nor post-mastectomy radiotherapy (PMRT) represents a contraindication to its use.

Refining the Performance of Sentinel Lymph Node Biopsy Post-neoadjuvant Chemotherapy in Patients with Pathologically Proven Pre-treatment Node-positive Breast Cancer: An Update for Clinical Practice.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has become the standard treatment regimen for locally advanced breast cancer and has recently been incorporated into the treatment of early breast cancer. It allows down-staging of tumors favoring breast-conservative surgery over mastectomy. Furthermore, NAC results in nodal conversion in about 40% of patients. This favorable outcome has complicated the decision-making regarding the best approach in managing the axilla post-treatment; especially in pathologically proven nodal disease prior to NAC. Axillary lymph node clearance is still the standard-of-care for this group of patients; however, it is clearly an over-treatment in a substantial number of patients. Given the high accuracy of sentinel lymph node biopsy (SLNB) post-NAC in clinically node-negative cases prior to treatment, substantial research has been carried out in order to validate the feasibility of post-NAC SLNB in pathologically proven node-positive cases. The results so far are still inconclusive, yet promising. MATERIALS AND METHODS: We performed a computer-aided review of the literature for relevant articles on the performance of SLNB post-NAC in pathologically proven node-positive patients prior to chemotherapy. We also targeted studies on important factors that can refine the accuracy of SLNB in this group of patients, as well as elements favoring pathological complete response. All studies focusing on post-NAC SLNB in pre-treatment node-positive cases including randomized controlled trials, retrospective and prospective series, review articles, and two meta-analyses were included. RESULTS: The review established a false-negative rate of 14-15.1% and an IR of 89-92.3%. Several technical enhancements, as well as imaging modalities, may be incorporated to improve the performance of SLNB. Furthermore, selected patients with more likelihood of pathological complete response represent the best candidates for this technique. CONCLUSION: SLNB is a valid option after NAC in patients with pathologically proven node-positive breast cancer, given the high node-conversion rate. The literature demonstrated a false-negative rate that is slightly higher than that of patients initially node-negative which although might increase the locoregional recurrence in theory, has no effect on chemotherapy-decision making, and will most probably have no impact on overall survival. We identified several measures to refine its accuracy.

Surgical treatment of the primary tumour improves the overall survival in patients with metastatic breast cancer: A systematic review and meta-analysis.

Traditionally, stage IV metastatic breast cancer has been treated with systemic therapy and/or radiotherapy in order to decrease cancer-associated symptoms, maintain quality of life and control disease burden. Previous research suggests that surgical treatment of the primary tumour may prolong survival, as well achieve local control of disease. Using the PubMed and Ovid SP databases, a literature review and meta-analysis was performed in order to assess whether surgical resection of the primary tumour in metastatic breast cancer prolongs survival. In this meta-analysis, a pooled hazard ratio of 0.63 (95% confidence interval, 0.58-0.7; P<0.0001) was revealed, equating to a 37% reduction in risk of mortality in patients that underwent surgical resection of the primary tumour. Therefore, it was concluded that surgery of the primary tumour in stage IV breast cancer appears to offer a survival benefit in metastatic patients.

Biological and synthetic mesh use in breast reconstructive surgery: a literature review.

Mesh use in surgical breast reconstruction is becoming increasingly common; however, there is still no consensus on whether synthetic matrices or biological matrices produce the best outcomes. This review analyses these outcomes, namely the differences in aesthetic outcomes, cost, and the rates of the most commonly reported complications.The results indicate that breast reconstruction with a synthetic matrix produces comparable aesthetic outcomes to a biological matrix, with lower costs and complication rates. The individual results for complication rates show that biological matrixes are associated with lower infection rates and slightly lower capsular contracture, but higher haematoma rates, and slightly higher rates of skin necrosis and explantation--although many had post-op radiotherapy.The majority of the studies evaluated used biological matrices, and there are no randomised controlled trials directly comparing the two types of meshes; definite conclusions cannot be drawn from the available evidence. The authors suggest that a randomised controlled trial comparing these outcomes in synthetic and biological matrix use is needed.

The role of death-associated protein 3 in apoptosis, anoikis and human cancer.

Death-associated protein 3 (DAP3) is a molecule with a significant role in the control of both apoptosis and anoikis. Apoptosis is the predominant type of programmed cell death (PCD) which may occur in response to irreparable damage to DNA, or in response to induction by inflammatory cells. Anoikis is subset of apoptosis which occurs in epithelial cells in response to detachment from the surrounding matrix. Both apoptosis and anoikis are of interest in the context of carcinogenesis. In this review, we shall discuss apoptosis and anoikis, and the recent literature regarding the role of DAP3 in both these pathways.