The Role of Human Epidermal Growth Factor Receptor 2 (HER2)-Targeted Therapies in Early-Stage Breast Cancer: Current Practices, Treatment De-escalation, and Future Prospects.

Human epidermal growth factor receptor 2 (HER2)-targeted therapy has transformed the treatment paradigm for early-stage HER2-positive breast cancer, providing personalized and effective interventions. This comprehensive review delves into the current state of HER2-targeted therapies, emphasizing pivotal clinical trials that have demonstrated their substantial impact on long-term outcomes. Combination therapies that integrate HER2-targeted agents with chemotherapy exhibit enhanced tumor responses, particularly in neoadjuvant settings. Neoadjuvant chemotherapy (NACT) is explored for its role in tumor downsizing, facilitating breast-conserving surgery (BCS), and incorporating oncoplastic solutions to address both oncologic efficacy and aesthetic outcomes. Innovative axillary management post-NACT, such as targeted axillary dissection (TAD), is discussed for minimizing morbidity. The review further explores the delicate balance between maximal therapy and de-escalation, reflecting recent trends in treatment approaches. The therapeutic landscape of HER2-low breast cancer is examined, highlighting considerations in HER2-positive breast cancer with BReast CAncer gene (BRCA) mutations. Emerging immunotherapeutic strategies, encompassing immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapy, are discussed in the context of their potential integration into treatment paradigms. In conclusion, the evolving landscape of HER2-positive early-stage breast cancer treatment, characterized by targeted therapies and multidisciplinary approaches, underscores the need for ongoing research and collaborative efforts. The aim is to refine treatment strategies and enhance patient outcomes in this dynamic and rapidly evolving field.

Evaluation of nipple aspirate fluid as a diagnostic tool for early detection of breast cancer.

There has been tremendous progress in detection of breast cancer in postmenopausal women, resulting in two-thirds of women surviving more than 20 years after treatment. However, breast cancer remains the leading cause of cancer-related deaths in premenopausal women. Breast cancer is increasing in younger women due to changes in life-style as well as those at high risk as carriers of mutations in high-penetrance genes. Premenopausal women with breast cancer are more likely to be diagnosed with aggressive tumours and therefore have a lower survival rate. Mammography plays an important role in detecting breast cancer in postmenopausal women, but is considerably less sensitive in younger women. Imaging techniques, such as contrast-enhanced MRI improve sensitivity, but as with all imaging approaches, cannot differentiate between benign and malignant growths. Hence, current well-established detection methods are falling short of providing adequate safety, convenience, sensitivity and specificity for premenopausal women on a global level, necessitating the exploration of new methods. In order to detect and prevent the disease in high risk women as early as possible, methods that require more frequent monitoring need to be developed. The emergence of "omics" strategies over the last 20 years, enabling the characterisation and understanding of breast cancer at the molecular level, are providing the potential for long term, longitudinal monitoring of the disease. Tissue and serum biomarkers for breast cancer stratification, diagnosis and predictive outcome have emerged, but have not successfully translated into clinical screening for early detection of the disease. The use of breast-specific liquid biopsies, such as nipple aspirate fluid (NAF), a natural secretion produced by breast epithelial cells, can be collected non-invasively for biomarker profiling. As we move towards an age of active surveillance, home-based liquid biopsy collection kits are increasingly being applied and these could provide a paradigm shift where NAF biomarker profiling is used for routine breast health monitoring. The current status of established and newly emerging imaging techniques for early detection of breast cancer and the potential for alternative biomarker screening of liquid biopsies, particularly those applied to high-risk, premenopausal women, will be reviewed.

Adjuvant Endocrine Therapy for Hormone-positive Breast Cancer, Focusing on Ovarian Suppression and Extended Treatment: An Update.

The benefits of five years of adjuvant endocrine therapy for oestrogen receptor (ER)-positive early breast cancer are well established. However, recent evidence suggests that extended endocrine treatment and ovarian suppression in selected groups of patients have significant advantages. In this article, we review the current evidence for adjuvant endocrine therapy in breast cancer with focus on extended adjuvant endocrine therapy and ovarian suppression, and also highlight the advantages and disadvantages of these therapeutic strategies. A literature search was performed through PubMed, Medline, and Cochrane using the following search terms: Endocrine therapy, Tamoxifen, Anastrazole, Ovarian Suppression, Exemestane, Letrozole and STS Inhibitors. All available evidence for adjuvant endocrine therapy was reviewed and summarised to assess the current guidance and the progress of the management of patients with ER-positive breast cancer. Extended endocrine therapy should be tailored according to patient needs dictated by their individual risk factors, molecular type of breast cancer, menopausal status, comorbidities, life style and risk of recurrence. Clinicians ought to discuss with patients the pros and cons of different adjuvant endocrine therapy approaches and highlight the potential side effects and toxicity.

Nipple aspirate fluid-A liquid biopsy for diagnosing breast health.

PURPOSE: Nipple secretions are protein-rich and a potential source of breast cancer biomarkers for breast cancer screening. Previous studies of specific proteins have shown limited correlation with clinicopathological features. Our aim, in this pilot study, was to investigate the intra- and interpatient protein composition of nipple secretions and the implications for their use as liquid biopsies. EXPERIMENTAL DESIGN: Matched pairs of nipple discharge/nipple aspirate fluid (NAF, n = 15) were characterized for physicochemical properties and SDS-PAGE. Four pairs were selected for semiquantitative proteomic profiling and trypsin-digested peptides analyzed using 2D-LC Orbitrap Fusion MS. The resulting data were subject to bioinformatics analysis and statistical evaluation for functional significance. RESULTS: A total of 1990 unique proteins were identified many of which are established cancer-associated markers. Matched pairs shared the greatest similarity (average Pearson correlation coefficient of 0.94), but significant variations between individuals were observed. CONCLUSIONS AND CLINICAL RELEVANCE: This was the most complete proteomic study of nipple discharge/nipple aspirate fluid to date providing a valuable source for biomarker discovery. The high level of milk proteins in healthy volunteer samples compared to the cancer patients was associated with galactorrhoea. Using matched pairs increased confidence in patient-specific protein levels but changes relating to cancer stage require investigation of a larger cohort.

Obesity-related hypertension and its remission following gastric bypass surgery - a review of the mechanisms and predictive factors.

It is well established that hypertension and obesity appear to be associated. The exact mechanism by which they are linked is unclear and remains a topic of a great deal of research. Current NICE guidelines recommend that patients with a BMI in excess of 35 kg/m(2) should be considered for bariatric surgery if they have a concomitant obesity-associated condition, of which hypertension is one. The commonest bariatric procedure in the UK is the Roux-en-Y gastric bypass, which has been shown to result in long-standing remission of hypertension in up to 93% of patients. This paper summarizes the existing literature on the main theories as to how obesity leads to hypertension as well as the literature concerning the effects of gastric bypass surgery on hypertension.

High TIMM17A expression is associated with adverse pathological and clinical outcomes in human breast cancer.

BACKGROUND: Mitochondrial dysfunction can be associated with genomic instability and has been implicated in the pathogenesis of several human malignancies, including breast cancer (BC). The mitochondrial protein, translocase of inner mitochondrial membrane 17 homolog A (TIMM17A) contributes to a pre-protein import complex, essential for mitochondrial function. In this study, TIMM17A mRNA expression was evaluated in benign and malignant breast tissues and correlated with pathological and clinical outcomes. METHODS: Breast cancer tissues (n = 127) and normal tissues (n = 33) underwent RNA extraction and reverse transcription, transcript levels were determined by using real-time quantitative PCR and normalized against CK19. Transcript levels were compared and then analysed against tumour size, tumour grade, oestrogen receptor (ER) status, nodal involvement, TNM stage, Nottingham prognostic index (NPI) and clinical outcome over a 10-year follow-up period. RESULTS: Compared to normal tissue (mean transcript level = 12.7), TIMM17A mRNA expression was higher in BC (62, p = 0.006), TNM-1 (37.9, p = 0.05), TNM-2 (114, p = 0.034), NPI-2 (81, p = 0.041), patients with progressive disease (169, p = 0.017) and those who died from BC (179, p = 0.026). Expression increased with tumour grade; grade 1 versus 2 (12.1 vs.70, p = 0.007), grade 1 versus 3 (12.1 vs.73, p = 0.065, [not significant] NS) and grade 1 versus 2 and 3 (12.1 vs. 72, p = 0.0048). Higher transcript levels were associated with ER-α positivity (94 vs. 31.6, p = 0.073, NS) and ER-ß negativity (82 vs. 16, p = 0.015). Nodal positivity was significantly associated with higher transcript levels (101 vs. 28.1, p = 0.046). Compared to disease-free patients (mean transcript level = 24.6), TIMM17A expression was significantly higher in those with progressive disease and patients who died of BC (179, p = 0.037). Higher transcript levels were significantly associated with poorer overall survival after a median follow-up of 10 years (p = 0.010). TIMM17A expression emerged as a strong independent predictor of overall survival in multivariate analysis (p = 0.033). CONCLUSION: TIMM17A mRNA expression is significantly associated with unfavourable pathological parameters including tumour grade, nodal positivity, TNM stage and NPI; in addition to adverse clinical outcomes such as progressive disease, disease-free and overall survival. TIMM17A offers utility as a prognostic marker and a novel mitochondrial target for potential therapeutic strategies.

Sentinel lymph node micrometastasis in human breast cancer: an update.

INTRODUCTION: The advent of sentinel lymph node biopsy (SLNB) and advances in histopathological and molecular analysis techniques have been associated with an increase in micrometastasis (MM) detection rate. However, the clinical significance of sentinel lymph node micrometastasis (SLN MM) continues to be a subject of much debate. In this article we review the literature concerning SLN MM, with particular emphasis on the prognostic significance of SLN MM. The controversies regarding histopathological assessment, clinical relevance and management implications are also discussed. METHODS: Literature review facilitated by Medline and PubMed databases. Cross referencing of the obtained articles was used to identify other relevant studies. RESULTS: Published studies have reported divergent and rather conflicting results regarding the clinical significance and implications of axillary lymph node (ALN) MM in general and SLN MM in particular. Some earlier studies demonstrated no associations, however most recent studies have found SLN MM to be an indicator of poorer prognosis and to be associated with non-SLN involvement. The use of adjuvant chemotherapy and/or hormonal manipulation therapy is associated with an improved survival in patients with SLN MM. Complete ALND may be safely omitted provided that adjuvant systemic therapy recommendations are equal to patients with node-positive disease. However, optimal management of SLN MM is yet to conclude. Furthermore, the identification of MM remains largely dependent on the analytical technique employed and the use of immunohistochemistry (IHC) increases the detection rate of SLN MM. Discrepancies in the histopathological interpretation of TNM classification of SLN tumour burden do exist. Published studies were non-randomized and have significant limitations including a small sample size, limited follow-up period, and lack of standardization and reproducibility of pathological examination of the SLN. CONCLUSION: Patients with SLN MM have a poorer prognosis than those who are SLN negative. Therapeutic recommendations regarding patients with SLN MM should be taken in the context of multidisciplinary team setting and in selected cases of SLN MM, complete ALND may be safely omitted. A better reproducibility of pathological interpretation of the TNM classification is required so that future therapeutic guidelines can be applied without confusion.

Risk-reducing strategies for women carrying BRCA1/2 mutations with a focus on prophylactic surgery.

BACKGROUND: Women who have inherited mutations in the BRCA1 or BRCA2 genes have substantially elevated risks of breast and ovarian cancer. Mutation carriers have various options, including extensive and regular surveillance, chemoprevention and risk-reducing surgery. The aim of this review is to provide an up-to-date analysis and to subsequently summarise the available literature in relation to risk-reducing strategies, with a keen focus on prophylactic surgery. METHODS: The literature review is facilitated by Medline and PubMed databases. The cross-referencing of the obtained articles was used to identify other relevant studies. RESULTS: Prophylactic surgery (bilateral mastectomy, bilateral salpingo-oophorectomy or a combination of both procedures) has proved to be the most effective risk-reducing strategy. There are no randomised controlled trials able to demonstrate the potential benefits or harms of prophylactic surgery; therefore, the evidence has been derived from retrospective and short follow-up prospective studies, in addition to hypothetical mathematical models.Based on the current knowledge, it is reasonable to recommend prophylactic oophorectomy for BRCA1 or BRCA2 mutation carriers when childbearing is completed in order to reduce the risk of developing breast and ovarian cancer. In addition, women should be offered the options of rigorous breast surveillance, chemoprevention with anti-oestrogens--especially for carriers of BRCA2--or bilateral prophylactic mastectomy. CONCLUSION: The selection of the most appropriate risk-reducing strategy is not a straightforward task. The impact of risk-reducing strategies on cancer risk, survival, and overall quality of life are the key criteria considered for decision-making. Notably, various other factors should be taken into consideration when evaluating individual mutation carriers' individual circumstances, namely woman's age, morbidity, type of mutation, and individual preferences and expectations.Although prospective randomised controlled trials concerned with examining the various interventions in relation to the woman's age and type of mutation are needed, randomisation is extremely difficult and rather deemed unethical given the current available evidence from retrospective studies.

Oestrogen-synthesising enzymes and breast cancer.

There is a large and compelling body of epidemiological and experimental evidence that oestrogens are the fuel behind the aetiology of breast cancer. The carcinogenic effects of oestrogen are postulated to be mediated by: the stimulation of cellular proliferation through their receptor-mediated hormonal activity. Other mechanisms include; direct genotoxic effects by increasing mutation rates through a cytochrome P450-mediated metabolic activation and induction of aneuploidy. The local biosynthesis of oestrogens, especially in postmenopausal women as a result of the interactions of various enzymes, is believed to play a very important role in the pathogenesis and development of hormone dependent breast carcinoma. The over-expression of such enzymes seems to be associated with the development of a more aggressive disease process, a poorer outcome and increased local and distant recurrences.

Oestrogen producing enzymes and mammary carcinogenesis: a review.

There is a large and compelling body of epidemiological and experimental evidence that oestrogens are instrumental in the aetiology of breast cancer. Their mechanisms of action are varied, including stimulation of cellular proliferation through receptor-mediated hormonal activity, increasing genetic mutation rates through cytochrome P450-mediated metabolic activation, and induction of aneuploidy. The local biosynthesis of oestrogens especially in postmenopausal women is believed to play a very important role in the pathogenesis and development of hormone dependent breast carcinoma and the over-expression of regulatory enzymes seems to be associated with the development of a more aggressive disease and associated with poor outcome and increased local and distant recurrences. In this article we highlight the role of CYP19 gene expression and aromatase activity in mammary carcinogenesis. Other oestrogen producing (17-beta-hydroxysteroid dehydrogenase and steroid sulphatase) and catalyzing enzymes (3-beta-hydroxysteroid dehydrogenase, Oestrogen sulfotransferase, CYP1A1, CYP1B1, and CYP3A4) are also discussed in some detail. Understanding the mechanisms that regulate these enzymes is crucial to the development of new endocrine therapies in post-menopausal females with hormone dependant breast cancer. Currently, third generation aromatase inhibitors has revolutionized the treatment of oestrogen dependant breast cancer. However, the important role of both STS and 17-beta-HSD type 1 in local oestrogen production provides novel potential targets for endocrine therapy. Such endocrine therapy is currently being explored and the development of STS inhibitors, combined aromatase/steroid sulfatase inhibitors and 17-beta-HSD type 1 inhibitors is underway with promising initial results.

The expression of gene transcripts of telomere-associated genes in human breast cancer: correlation with clinico-pathological parameters and clinical outcome.

BACKGROUND: Telomerase is a ribonucleoprotein enzyme that synthesises telomeres in human germ cells, embryogenesis and in cancer, maintaining chromosomal length, stability and cellular immortality. The hTERT gene is the rate-limiting determinant of telomerase reactivation during immortalization and malignant transformation. Telomeric DNA-binding proteins have been attracting increasing interest due to their essential role in the regulation of telomeric DNA length and in protecting against chromosomal end-to-end fusion. These proteins include hTR, TRF1, TRF2, TANK1, TANK2, POT1, TIN2, EST1, and TEP. This study represents the first comprehensive investigation of the mRNA expression of key telomere-related genes in human breast cancer. METHODS: One hundred and twenty seven tumour tissues and 33 normal tissues were analyzed. Levels of transcription of hTERT, hTR, TRF1, TRF2, TANK1, TANK2, POT1, TIN2, EST1, and TEP1 were determined using real-time quantitative PCR. The mRNA expression of these genes was normalized against CK19 and was then analyzed against the pathological parameters and clinical outcome over a 10 year follow up period. RESULTS: The mRNA expressions of hTERT, hTR, TANK1, EST1, and TEP1 were higher in tumour samples compared with normal breast tissue. This reached statistical significance for EST1 when comparing good prognosis tumours with normal breast tissue (means=11013 vs 1160, P=0.05). Both hTERT and TEP1 levels significantly predicted overall survival (P=0.012 and 0.005 respectively) and disease-free survival (P=0.0011 and 0.01 respectively). The mRNA levels of TANK2 and POT1 were lower in malignant tissues compared with non-malignant breast tissues and this difference reached statistical significance when comparing the levels in normal tissues with those in advanced tumours (P=0.0008 and P=0.038 respectively). Their levels fell further with increasing tumour's stage and were higher in tumours from patients who remained disease free compared with those who developed local recurrence or distant metastasis or died from breast cancer.TRF2 showed a trend similar to that of TANK2 and POT1. Furthermore, there was a highly significant correlation between TANK1 expression and that of hTERT, hTR, TRF1, TRF2 and EST1, (r=0.533, 0.586, 0.608, 0.644 and 0.551 respectively, P<0.001). CONCLUSIONS: Genes encoding telomere-associated proteins display different patterns of mRNA expression in human breast cancer, and in normal breast tissue, suggesting different and sometimes opposing roles in mammary carcinogenesis. hTERT, hTR, TANK1, EST1 and TEP1 seem to be up-regulated, with hTERT and TEP1 correlating with clinical outcome. Conversely, TANK2 and POT1 transcription levels demonstrate a compelling trend to be lower in malignant tissues and lower still in those patients who develop recurrent disease suggesting that TANK2 and POT1 may act as tumour suppressor genes possibly by negatively regulating telomerase activity.

The role of cyclooxygenase-2 in breast cancer: review.

There is a growing body of evidence that COX-2 expression s a fundamental step in breast cancer pathogenesis acting through prostaglandin-dependent and independent mechanisms. Epidemiological studies suggest that NSAIDs confer a moderate degree of benefit against breast cancer. However further work is required to establish how this enzyme system can be best manipulated for therapeutic benefit.

The expression of hTR and hTERT in human breast cancer: correlation with clinico-pathological parameters.

BACKGROUND: Telomerase is a ribonucleoprotein enzyme that synthesizes telomeres after cell division and maintains chromosomal stability leading to cellular immortalization. Telomerase has been associated with negative prognostic indicators in some studies. The present study aims to detect any association between telomerase sub-units: hTERT and hTR and the prognostic indicators including tumour's size and grade, nodal status and patient's age. METHODS: Tumour samples from 46 patients with primary invasive breast cancer and 3 patients with benign tumours were collected. RT-PCR analysis was used for the detection of hTR, hTERT, and PGM1 (as a housekeeping) genes expression. RESULTS: The expression of hTR and hTERT was found in 31(67.4%) and 38 (82.6%) samples respectively. We observed a significant association between hTR gene expression and younger age at diagnosis (p = 0.019) when comparing patients < or = 40 years with those who are older than 40 years. None of the benign tumours expressed hTR gene. However, the expression of hTERT gene was revealed in 2 samples. No significant association between hTR and hTERT expression and tumour's grade, stage and nodal status was seen. CONCLUSION: The expression of hTR and hTERT seems to be independent of tumour's stage. hTR expression probably plays a greater role in mammary tumourogenesis in younger women (< or = 40 years) and this may have therapeutic implications in the context of hTR targeting strategies.

Impact of delay on survival in patients with ruptured abdominal aortic aneurysm.

Rupture of the abdominal aortic aneurysm (RAAA) is a common surgical emergency. Surgical treatment of this condition carries a high morbidity and mortality rate. For successful outcome, an early diagnosis and prompt treatment are essential. However, recently, some centers have reported better results in patients whose surgery had been delayed because of interhospital transfer. Delay in treatment sometimes occurs as patients are transferred from one institution to another where specialized vascular care is available. This retrospective study sought to determine the effect of delay in treatment on the mortality of patients with RAAA repair.The time from arrival at the emergency room to surgery and operative time were obtained from the case notes of 45 consecutive patients with RAAA. Patients' physiology scores on admission were calculated using V-POSSUM for the RAAA model.Thirty-five patients were diagnosed with RAAA in the emergency room and were transferred to surgery. These patients were divided into two groups: patients who had surgery within 1 hour (n = 23) and those in whom surgery was delayed for up to 4 hours (n = 12). There was no significant difference in physiology score between the two groups (p = .12). The time to surgery and operative time with death as the outcome were plotted on a logistic regression model that showed that the delay in surgical treatment increases the mortality rate following RAAA repair (p = .041). Furthermore, a long operative time was associated with a higher surgical mortality rate (p = .029). Delay to surgery and a long operation increase the mortality rate following RAAA repair. However, delay to surgery alone did not influence the mortality rate.

The association between telomerase activity and expression of its RNA component (hTR) in breast cancer patients: the importance of DNase treatment.

Telomerase is a ribonucleoprotein enzyme that compensates for the telomere length shortening which occurs during the cell cycle. Telomerase activity has been detected in most tumours but not in somatic cells. However, hTR; the RNA component of telomerase; has been reported to be universally expressed in both cancerous and non-cancerous tissues. Tumour samples from 50 patients with primary invasive breast cancer were collected. The TRAP assay was used to detect telomerase activity. RT-PCR on cDNA and DNased cDNA samples and control groups was used to detect the expression of hTR, GAPDH and PGM1 genes. Seventy-two percent of samples showed telomerase activity. DNA contamination was detected in 36 (72%) of RNA samples. Without performing DNase treatment, 49 (98%) of all samples showed hTR expression, but with the application of this strategy, hTR expression decreased from 98% to 64%. A significant association (p < 0.001) between hTR expression and telomerase activity was observed. Among the 32 hTR positive samples, 30 had telomerase activity and among the 18 hTR negative samples, telomerase activity was observed in 6 cases. Thus the application of this strategy could provide an applicable tool to use instead of the TRAP assay thus facilitating telomerase research in cancer genetic investigations.

The facial skin lesions "see and treat" clinic: A prospective study.

Facial lesions are commonly referred to ear, nose and throat surgeons. Almost all are amenable to excision under local anaesthetic as a day case. However, in the UK, there is still a significant delay between referral by the general practitioner (GP) and final surgery. To address this delay, a one stop see and treat consultant led clinic was set up in the community. The aim of this study was to assess the impact of the one stop clinic on waiting times and to ascertain the satisfaction of patients with the treatment they received in this clinic. Patients with facial skin lesions were referred by the GPs to the ENT department in the usual manner. The referral letters were screened by two consultants, the appointments were booked by telephone and the patients were seen and treated in a single visit. The clinics were held in a minor surgery unit of a centrally located GP practice. Patients were seen, assessed and if the facial lesion was considered amenable to excision under local anaesthetic, the patient was consented and the procedures carried out immediately. The clinic was audited over a 1 year period. Waiting times were compared before and after the start of the project. Patients were asked to fill in a questionnaire immediately after surgery. The attendance rate was 96%. The waiting time was reduced from 121 to 47 days. Patients rated the clinic experience as excellent (88%) or good (12%) indicating a very high satisfaction rate. During the study period, 160 lesions were excised of which 22% were malignant. Patients with malignant lesions did not show any sign of recurrence at a follow up of 9 months, except in one case with basal cell carcinoma. This was operated on and removed completely. Our project shows that the aims of reducing waiting times and improving patient care were achieved with this community model of a one stop facial lesions clinic. This clinic is now an integral part of the service provided by the ear, nose and throat department at Ipswich hospital, UK.

Skin-sparing mastectomy and immediate breast reconstruction: patient satisfaction and clinical outcome.

BACKGROUND: Skin-sparing mastectomy (SSM) followed by immediate reconstruction has been advocated as an effective treatment option for patients with early-stage breast carcinoma. It minimizes deformity and improves cosmesis through preservation of the natural skin envelope of the breast. The purpose of this study was to evaluate postoperative morbidity, patients' satisfaction, and oncological safety for SSM and immediate breast reconstruction (IBR) with a latissimus dorsi (LD) myocutaneous flap and/or breast prosthesis in patients with operable breast cancer. METHODS: Twenty-one consecutive patients with operable breast cancer undergoing 25 SSM and immediate reconstruction with an LD flap plus implant (n = 14) or implant alone (n = 11) were retrospectively studied (from 2001 through 2005). The median patients' age was 44 years (range, 30-68). Patient satisfaction with the outcome of surgery was assessed using a detailed questionnaire including a linear visual analogue scale ranging from 0 (not satisfied) to 10 (most satisfied). Eight of 20 (40%) patients required adjuvant chemotherapy, and only 2 patients required post-mastectomy radiation. Reconstruction of the nipple-areola complex was performed in 7 patients (33%) using the trefoil local flap technique. Contralateral procedures to achieve symmetry were performed in 6 (28%) patients (5 augmentations and 1 reduction mammoplasty). RESULTS: Histological analysis showed pure ductal carcinoma in situ (DCIS) in 4 patients and invasive carcinoma (+/- DCIS) in 20 cases, of which 5 (25%) were node positive. One prophylactic mastectomy in a BRCA-2 carrier was negative for malignancy. Tumor size ranged from 5 to 90 mm. The surgical margins were clear in all cases. There was no delay in time to commencement of adjuvant therapies. After a mean follow-up period of 13.5 months (range, 5-46 months), none of the patients developed locoregional recurrence. Only 1 patient (5%) developed systemic recurrence (bony metastases). Overall survival was 100%. The incidence of flap necrosis/loss, implant loss, wound infection, or hematoma requiring surgical evacuation was 0%, 0%, 0%, and 0%, respectively. Capsule formation requiring capsulotomy was observed in 3 of 21 patients (14%). The median patient satisfaction score was 10 (range, 6-10). CONCLUSION: SSM and IBR for operable breast cancer is associated with a high level of patient satisfaction and low morbidity. The procedure seems to be oncologically safe, even in patients with high-risk (T3 or node-positive) carcinoma. The latter needs to be confirmed with greater numbers of patients and longer follow-up.