Atypical Ductal Hyperplasia of the Breast on Core Needle Biopsy: Risk of Malignant Upgrade on Surgical Excision.

PURPOSE: This study identified factors predicting malignant upgrade for atypical ductal hyperplasia (ADH) diagnosed on core-needle biopsy (CNB) and developed a nomogram to facilitate evidence-based decision making. METHODS: This retrospective analysis included women diagnosed with ADH at the National Cancer Centre Singapore (NCCS) in 2010-2015. Cox proportional hazards regression was used to identify clinical, radiological, and histological factors associated with malignant upgrade. A nomogram was constructed using variables with the strongest associations in multivariate analysis. Multivariable logistic regression coefficients were used to estimate the predicted probability of upgrade for each factor combination. RESULTS: Between 2010 and 2015, 238,122 women underwent mammographic screening under the National Breast Cancer Screening Program. Among 29,564 women recalled, 5,971 CNBs were performed. Of these, 2,876 underwent CNBs at NCCS, with 88 patients (90 lesions) diagnosed with ADH and 26 lesions upgraded to breast malignancy on excision biopsy. In univariate analysis, factors associated with malignant upgrade were the presence of a mass on ultrasound (p = 0.018) or mammography (p = 0.026), microcalcifications (p = 0.047), diffuse microcalcification distribution (p = 0.034), mammographic parenchymal density (p = 0.008). and ≥ 3 separate ADH foci found on biopsy (p = 0.024). Mammographic parenchymal density (hazard ratio [HR], 0.04; 95% confidence interval [CI], 0.005-0.35; p = 0.014), presence of a mass on ultrasound (HR, 10.50; 95% CI, 9.21-25.2; p = 0.010), and number of ADH foci (HR, 1.877; 95% CI, 1.831-1.920; p = 0.002) remained significant in multivariate analysis and were included in the nomogram. CONCLUSION: Our model provided good discrimination of breast cancer risk prediction (C-statistic of 0.81; 95% CI, 0.74-0.88) and selected for a subset of women at low risk (2.1%) of malignant upgrade, who may avoid surgical excision following a CNB diagnosis of ADH.

Fatty acid oxidation is a druggable gateway regulating cellular plasticity for driving metastasis in breast cancer.

Cell state transitions control the functional behavior of cancer cells. Epithelial-to-mesenchymal transition (EMT) confers cancer stem cell-like properties, enhanced tumorigenicity and drug resistance to tumor cells, while mesenchymal-epithelial transition (MET) reverses these phenotypes. Using high-throughput chemical library screens, retinoids are found to be potent promoters of MET that inhibit tumorigenicity in basal-like breast cancer. Cell state transitions are defined by reprogramming of lipid metabolism. Retinoids bind cognate nuclear receptors, which target lipid metabolism genes, thereby redirecting fatty acids for ß-oxidation in the mesenchymal cell state towards lipid storage in the epithelial cell state. Disruptions of key metabolic enzymes mediating this flux inhibit MET. Conversely, perturbations to fatty acid oxidation (FAO) rechannel fatty acid flux and promote a more epithelial cell phenotype, blocking EMT-driven breast cancer metastasis in animal models. FAO impinges on the epigenetic control of EMT through acetyl-CoA-dependent regulation of histone acetylation on EMT genes, thus determining cell states.

Genetic differences between benign phyllodes tumors and fibroadenomas revealed through targeted next generation sequencing.

Breast fibroepithelial lesions are biphasic tumors which comprise the common benign fibroadenomas (FAs) and the rarer phyllodes tumors (PTs). This study analyzed 262 (42%) conventional FAs, 45 (7%) cellular FAs, and 321 (51%) benign PTs contributed by the International Fibroepithelial Consortium, using a previously curated 16 gene panel. Benign PTs were found to possess a higher number of mutations, and higher rates of cancer driver gene alterations than both groups of FAs, in particular MED12, TERT promoter, RARA, FLNA, SETD2, RB1, and EGFR. Cases with MED12 mutations were also more likely to have TERT promoter, RARA, SETD2, and EGFR. There were no significant differences detected between conventional FAs and cellular FAs, except for PIK3CA and MAP3K1. TERT promoter alterations were most optimal in discriminating between FAs and benign PTs. Our study affirms the role of sequencing and key mutations that may assist in refining diagnoses of these lesions.

Impact of hormonal status on ductal carcinoma in situ of the breast: Outcome and prognostic factors.

Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous disease which is increasingly diagnosed through improved screening measures. Multiple prognostic scores have been devised to predict the risk of local recurrence (LR), and the optimal adjuvant management for DCIS is still debated. Hence, the aim of this analysis is to investigate the factors contributing to the prognosis of DCIS, in particular the role of its hormonal status. From 2005 to 2016, a total of 1221 female patients diagnosed with DCIS at the National Cancer Centre Singapore and Singapore General Hospital were studied. The mean age of diagnosis was 54 years of age (sd = 11.0), with estrogen receptor (ER)-positive DCIS tumors presenting earlier (mean age 54 vs 57 years of age; P < .001). DCIS with negative hormonal status (HS) correlates significantly with a larger size (mean 23.5mm vs 13.0 mm, P < .001) and higher grade of tumor (P < .001). Patients with positive HS were more likely to undergo breast conservation surgery over a mastectomy, in contrast to patients with negative HS (P < .001). Patients with negative HS had a poorer prognosis, with a shorter time of overall survival time (HR = 26.3, P = .020). In conclusion, our study shows that the hormonal status, age of diagnosis, and positive margins are important prognostic factors for DCIS, at least in our Asian population.

A Circulating miRNA Signature for Stratification of Breast Lesions among Women with Abnormal Screening Mammograms.

Although mammography is the gold standard for breast cancer screening, the high rates of false-positive mammograms remain a concern. Thus, there is an unmet clinical need for a non-invasive and reliable test to differentiate between malignant and benign breast lesions in order to avoid subjecting patients with abnormal mammograms to unnecessary follow-up diagnostic procedures. Serum samples from 116 malignant breast lesions and 64 benign breast lesions were comprehensively profiled for 2,083 microRNAs (miRNAs) using next-generation sequencing. Of the 180 samples profiled, three outliers were removed based on the principal component analysis (PCA), and the remaining samples were divided into training (n = 125) and test (n = 52) sets at a 70:30 ratio for further analysis. In the training set, significantly differentially expressed miRNAs (adjusted p < 0.01) were identified after correcting for multiple testing using a false discovery rate. Subsequently, a predictive classification model using an eight-miRNA signature and a Bayesian logistic regression algorithm was developed. Based on the receiver operating characteristic (ROC) curve analysis in the test set, the model could achieve an area under the curve (AUC) of 0.9542. Together, this study demonstrates the potential use of circulating miRNAs as an adjunct test to stratify breast lesions in patients with abnormal screening mammograms.

A novel genomic panel as an adjunctive diagnostic tool for the characterization and profiling of breast Fibroepithelial lesions.

BACKGROUND: Known collectively as breast fibroepithelial lesions (FELs), the common fibroadenomas (FAs) and the rarer phyllodes tumors (PTs) are a heterogenous group of biphasic neoplasms. Owing to limited tissue availability, inter-observer variability, overlapping histological features and heterogeneity of these lesions, diagnosing them accurately on core biopsies is challenging. As the choice management option depends on the histological diagnosis; a novel 16-gene panel assay was developed to improve the accuracy of preoperative diagnosis on core biopsy specimens. METHODS: Using this 16-gene panel, targeted amplicon-based sequencing was performed on 275 formalin-fixed, paraffin-embedded (FFPE) breast FEL specimens, archived at the Singapore General Hospital, from 2008 to 2012. RESULTS: In total, 167 FAs, 24 benign, 14 borderline and 6 malignant PTs, were profiled. Compared to FAs, PTs had significantly higher mutation rates in the TERT promoter (p <  0.001), RARA (p <  0.001), FLNA, RB1 and TP53 (p = 0.002, 0.020 and 0.018, respectively). In addition to a higher mutational count (p <  0.001), TERT promoter (p <  0.001), frameshift, nonsense and splice site (p = 0.001, < 0.001 and 0.043, respectively) mutations were also frequently observed in PTs. A multivariate logistic regression model was built using these as variables and a predictive scoring system was developed. It classifies a FEL at low or high risk (score <  1 and ≥ 1, respectively) of being a PT. This scoring system has good discrimination (ROC area = 0.773, 95% CI: 0.70 to 0.85), calibration (p = 0.945) and is significant in predicting PTs (p <  0.001). CONCLUSION: This novel study demonstrates the ability to extract DNA of sufficient quality and quantity for targeted sequencing from FFPE breast core biopsy specimens, along with their successful characterization and profiling using our customized 16-gene panel. Prospective work includes validating the utility of this promising 16-gene panel assay as an adjunctive diagnostic tool in clinical practice.

Genomic characterisation of breast fibroepithelial lesions in an international cohort.

Fibroepithelial lesions (FELs) are a heterogeneous group of tumours comprising fibroadenomas (FAs) and phyllodes tumours (PTs). Here we used a 16-gene panel that was previously discovered to be implicated in pathogenesis and progression, to characterise a large international cohort of FELs via targeted sequencing. The study comprised 303 (38%) FAs and 493 (62%) PTs which were contributed by the International Fibroepithelial Consortium. There were 659 (83%) Asian and 109 (14%) non-Asian FELs, while the ethnicity of the rest was unknown. Genetic aberrations were significantly associated with increasing grade of PTs, and were detected more in PTs than FAs for MED12, TERT promoter, RARA, FLNA, SETD2, TP53, RB1, EGFR, and IGF1R. Most borderline and malignant PTs possessed ≥ 2 mutations, while there were more cases of FAs with ≤ 1 mutation compared to PTs. FELs with MED12 mutations had significantly higher rates of TERT promoter, RARA, SETD2, EGFR, ERBB4, MAP3K1, and IGF1R aberrations. However, FELs with wild-type MED12 were more likely to express TP53 and PIK3CA mutations. There were no significant differences observed between the mutational profiles of recurrent FAs, FAs with a history of subsequent ipsilateral recurrence or contralateral occurrence, and FAs without a history of subsequent events. We identified recurrent mutations which were more frequent in PTs than FAs, with borderline and malignant PTs harbouring cancer driver gene and multiple mutations. This study affirms the role of a set of genes in FELs, including its potential utility in classification based on mutational profiles. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Isolated invasive ductal carcinoma of the nipple-areolar complex: A rare occurrence yet to be reported in current literature.

Invasive ductal carcinoma of the nipple-areolar complex is exceedingly rare. Patients who present with bloody nipple discharge with or without the presence of Paget's disease constitute one-third of all symptomatic in situ patients. Only rarely does an invasive cancer cause nipple discharge in the absence of a clinical mass. Even more obscure is the case of the invasive cancer involving solely the nipple-areolar complex. Sir James Paget first described 'an eczematous change in the skin of the nipple preceding an underlying mammary cancer' in 1874, which is now known as Paget's disease, considered to be ductal carcinoma in situ of the nipple-areolar region. There are two competing theories as to the pathogenesis of Paget's disease of the breast-one suggests that Pagetoid cells are keratinocytes that have undergone malignant transformation. According to this theory, Paget's disease of the breast represents an in situ carcinoma of the skin-and that overlying skin changes and underlying malignancy are discontinuous. The second theory suggests that cells migrate along basement membranes and enter the epidermis and dermis of the nipple-areola complex. Pagetoid cells and underlying carcinomas demonstrate similar immunohistochemical staining patterns.

Behaviour and characteristics of low-grade ductal carcinoma in situ of the breast: literature review and single-centre retrospective series.

AIMS: Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous disease that has risen to prominence and more recently controversy, with the advent of screening mammography. Debate concerning the true biological potential of low nuclear grade DCIS continues to challenge therapeutic considerations. In this study, we carried out a comprehensive literature review of the behaviour, outcomes and current management trials of low-grade DCIS, as well as a retrospective study of a large single institutional series of low-grade DCIS diagnosed at our hospital. METHODS AND RESULTS: The study cohort comprised 195 cases of low-grade DCIS diagnosed at the Singapore General Hospital from 1994 to 2010. Clinicopathological parameters and follow-up data were retrieved and compared between screen-detected and symptomatic low-grade DCIS. Immunohistochemistry was performed for ER, PR and HER2. Among 195 cases, 123 (63.1%) were screen-detected, while 72 (36.9%) were symptomatic. Screen-detected cases had frequent calcifications (P < 0.001) and were smaller (P = 0.018) than symptomatic cases. All cases were ER-positive and rate of PR expression was high. No HER2 overexpression was observed. Mean and median follow-up periods were 107.8 and 109.6 months, respectively. Six patients recurred ipsilaterally, and one patient developed direct distant metastasis. One breast cancer-related death was recorded. Positive surgical margins (P = 0.023) were significantly associated with a higher risk of ipsilateral recurrences, as well as poorer disease-free survivals (P = 0.010). CONCLUSION: Our data indicate that low-grade DCIS may be followed by invasive recurrences and even metastatic disease, requiring more study before being regarded as innocuous and indolent.

Surgical and oncological safety of nipple-sparing mastectomy in an Asian population.

BACKGROUND: Nipple-sparing mastectomy (NSM) allows for excellent postmastectomy reconstruction aesthetics and is used for both therapeutic and risk-reducing purposes. Reservations regarding the potential for locoregional recurrence and concerns about nipple-areolar complex (NAC) necrosis remain amongst many surgeons. We review the surgical and oncological outcomes after NSM in our institution. METHODS: All NSM cases at the National Cancer Centre Singapore and Singapore General Hospital between 2005 and 2015 were reviewed. Tumour characteristics, reconstruction methods, surgical and oncological outcomes are described. RESULTS: A total of 139 NSMs were performed for 130 patients. The median age was 46 years (range 21-66). The use of NSM increased from 2% of all breast reconstructions in 2005 to 37% in 2015. The majority (n = 119; 86%) were for cancer treatment and 20 (14%) for risk-reducing purposes. Among those performed for cancer, patients mainly had early stage breast cancer (n = 106, 89%). Autologous reconstruction (n = 111, 80%) was most common. Early complications requiring surgical intervention occurred in 24 (17%) NSMs, including 9 partial/complete flap loss and 2 complete NAC loss. Smoking, previous breast radiation and periareolar incision were all not associated with a higher re-intervention rate (p = 0.93, 0.41 and 0.91, respectively). Median follow-up was 43 months (range 5-145). Five patients (4%) developed local recurrence, including 2 NAC recurrences. The 2- and 5-year overall survival rate is 97 and 90%, respectively. CONCLUSION: NSM is an oncologically safe procedure in selected patients with acceptable low complication rates.

Genomic profile of breast sarcomas: a comparison with malignant phyllodes tumours.

PURPOSE: We aimed to investigate the genomic profile of breast sarcomas (BS) and compare with that of malignant phyllodes tumours (MPT). METHODS: DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) specimens from 17 cases of BS diagnosed at Singapore General Hospital from January 1991 to December 2014. Targeted deep sequencing and copy number variation (CNV) analysis on 16 genes, which included recurrently mutated genes in phyllodes tumours and genes associated with breast cancer, were performed on these samples. Genetic alterations (GA) observed were summarised and analysed. RESULTS: Nine cases met the quality control requirements for both targeted deep sequencing and CNV analysis. Three (33.33%) were angiosarcomas and 6 (66.67%) were non-angiosarcomas. In the non-angiosarcoma group, 83.33% (n = 5) of the patients had GA in the TERT gene. The other commonly mutated genes in this group of tumours were MED12 (n = 4, 66.67%), BCOR (n = 4, 66.67%), KMT2D (n = 3, 50%), FLNA (n = 3, 50%) and NF1 (n = 3, 50%). In contrast, none of the angiosarcomas had mutations or copy number alterations in TERT, MED12, BCOR, FLNA or NF1. Eighty percent of patients with GA in TERT (n = 5) had concurrent mutations in MED12. Sixty percent (n = 3) of these cases also demonstrated GA in NF1, PIK3CA or EGFR which are known cancer driver genes. CONCLUSIONS: The non-angiosarcoma group of BS was found to share similar GA as those described for MPT, which may suggest a common origin and support their consideration as a similar group of tumours with regard to management and prognostication.

Bilateral breast cancers in an Asian population, and a comparison between synchronous and metachronous tumours.

BACKGROUND: Women with unilateral breast cancer have an increased risk of developing bilateral breast cancer (BBC). Patients with metachronous BBC (mBBC) usually have an earlier age of onset, and their prognoses have been shown to be either similar or poorer than those with synchronous BBC (sBBC). Given the differing presentation and characteristics of breast cancers in the Asian population and the West, this study aims to characterize Asian patients with BBC. METHODS: All patients who had oncological breast surgery between 2001 and 2010 at the Singapore General Hospital and National Cancer Centre Singapore were reviewed. Patients with BBC were identified and studied. RESULTS: A total of 5520 Singaporean women had oncological breast surgery, 155 women (2.8%) had BBC. Of those with BBC, 47.1% (n = 73) were synchronous and 52.9% (n = 82) metachronous (mean interval of 39.4 months), and there was no difference in median age in both groups (54 years of age). Patients with sBBC were more likely to have a positive family history and had asymptomatic contralateral tumours. Although patients with sBBCs were more likely to have ER/PR positive and Her2 negative tumours, they had a lower 5-year overall survival than those with mBBC (P = 0.022). CONCLUSION: Our study shows that Asian women with BBC have different characteristics to their Western counterparts. In particular, women with sBBC tended to have a lower 5-year overall survival compared to those with mBBC, despite having seemingly biologically favourable tumours, which suggest that there may be more underlying their tumour biology and genetics.

Breast cancer in women with neurofibromatosis type 1 (NF1): a comprehensive case series with molecular insights into its aggressive phenotype.

PURPOSE: The purpose of the study was to improve the understanding of NF1-associated breast cancer, given the increased risk of breast cancer in this tumour predisposition syndrome and the limited data. METHODS: We identified 18 women with NF1 and breast cancer at our institution. Clinical and pathologic characteristics of NF1-associated breast cancers were compared with 7132 breast cancers in patients without NF1 from our institutional database. Next generation sequencing was performed on DNA from blood and breast cancer specimens available. Blood specimens negative for NF1 mutation were subjected to multiplex ligation-dependent probe amplification (MLPA) to identify complete/partial deletions or duplications. Expression of neurofibromin in the NF1-associated breast cancers was evaluated using immunohistochemistry. RESULTS: There was a higher frequency of grade 3 (83.3% vs 45.4%, p = 0.005), oestrogen receptor (ER) negative (66.7% vs 26.3%, p < 0.001) and human epidermal growth factor receptor 2 (HER2)-positive (66.7% vs 23.4%, p < 0.001) tumours among NF1 patients compared to non-NF1 breast cancers. Overall survival was inferior in NF1 patients in multivariable analysis (hazard ratio 2.25, 95% CI 1.11-4.60; p = 0.025). Apart from germline NF1 mutations (11/16; 69%), somatic mutations in TP53 (8/10; 80%), second-hit NF1 (2/10; 20%), KMT2C (4/10; 40%), KMT2D (2/10; 20%), and PIK3CA (2/10; 20%) were observed. Immunohistochemical expression of neurofibromin was seen in the nuclei and/or cytoplasm of all specimens, but without any consistent pattern in the intensity or extent. CONCLUSIONS: This comprehensive series of NF1-associated breast cancers suggests that their aggressive features are related to germline NF1 mutations in cooperation with somatic mutations in TP53, KMT2C and other genes.

Immediate breast reconstruction following nipple-sparing mastectomy in an Asian population: Aesthetic outcomes and mitigating nipple-areolar complex necrosis.

BACKGROUND: Nipple-sparing mastectomies (NSMs) are increasingly performed to obtain the best aesthetic and psychological outcomes in breast cancer treatment. However, merely preserving the nipple-areolar complex (NAC) does not guarantee a good outcome. Darkly pigmented NACs and a tendency for poor scarring outcomes are particular challenges when treating Asian patients. Herein, we review the reconstructive outcomes following NSM at Singapore General Hospital. METHODS: All breasts reconstructed following NSM over an 11-year period from 2005 to 2015 were reviewed. Information was collected from the patients' records on mastectomy indications, operative details, and complications. Patient satisfaction, breast sensation, and aesthetic outcomes were evaluated in 15 patients. Sensation was quantified using the Semmes-Weinstein monofilament test. RESULTS: A total of 142 NSMs were performed in 133 patients for breast cancer (n=122, 85.9%) or risk reduction (n=20, 14.1%). Of the procedures, 114 (80.2%) were autologous reconstructions, while 27 (19.0%) were reconstructions with implants. Complications occurred in 28 breasts (19.7%), with the most common complication being NAC necrosis, which occurred in 17 breasts (12.0%). Four breasts (2.8%) had total NAC necrosis. The overall mean patient satisfaction score was 3.0 (good). The sensation scores were significantly diminished in the skin envelope, areola, and nipple of breasts that had undergone NSM compared to non-operated breasts (P<0.05). Half of the subset of 15 patients in whom aesthetic outcomes were evaluated had reduced nipple projection. CONCLUSIONS: Immediate reconstruction after NSM was performed with a low complication rate in this series, predominantly through autologous reconstruction. Patients should be informed of potential drawbacks, including NAC necrosis, reduced nipple projection, and diminished sensation.

Evaluation of three polygenic risk score models for the prediction of breast cancer risk in Singapore Chinese.

Genome-wide association studies (GWAS) have proven highly successful in identifying single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. The majority of these studies are on European populations, with limited SNP association data in other populations. We genotyped 51 GWAS-identified SNPs in two independent cohorts of Singaporean Chinese. Cohort 1 comprised 1294 BC cases and 885 controls and was used to determine odds ratios (ORs); Cohort 2 had 301 BC cases and 243 controls for deriving polygenic risk scores (PRS). After age-adjustment, 11 SNPs were found to be significantly associated with BC risk. Five SNPs were present in <1% of Cohort 1 and were excluded from further PRS analysis. To assess the cumulative effect of the remaining 46 SNPs on BC risk, we generated three PRS models: Model-1 included 46 SNPs; Model-2 included 11 statistically significant SNPs; and Model-3 included the SNPs in Model-2 but excluded SNPs that were in strong linkage disequilibrium with the others. Across Models-1, -2 and -3, women in the highest PRS quartile had the greatest ORs of 1.894 (95% CI = 1.157-3.100), 2.013 (95% CI = 1.227-3.302) and 1.751 (95% CI = 1.073-2.856) respectively, suggesting a direct correlation between PRS and BC risk. Given the potential of PRS in BC risk stratification, our findings suggest the need to tailor the selection of SNPs to be included in an ethnic-specific PRS model.

Surgery for early breast cancer in the extremely elderly leads to improved outcomes - An Asian population study.

AIM: The optimal treatment of breast cancer for extremely elderly patients (aged ≥ 80 years) is debatable. With an aging population, management of this group of patients will be increasingly common. This study aims to compare the survival outcomes of extremely elderly patients against younger ones, following different treatment modalities within each stage. The differences in treatment patterns across different stages have also been examined. METHODS: Female Singapore Citizens and Permanent Residents diagnosed with breast cancer from 2003 to 2014 were identified from the Singapore Cancer Registry. Patients were divided into 2 age groups, below 80, and 80 and above years old, and categorized into 3 main treatment groups, namely surgery, non-surgical treatment, and no treatment. Analysis was made on their survival outcomes. RESULTS: 19,314 patients were diagnosed with breast cancer during the 12-year study period. 1482 patients were excluded due to unknown stage. 673 patients were aged 80 years and above, while 17,159 patients were aged below 80. Elderly patients presented with later stages of disease, and were less likely to have surgery. In Stage I and II, the difference in 5-year breast cancer specific outcome following surgery, was small between the 2 age groups. Among the elderly group, surgery resulted in improved survival. Those who did not have surgery performed better with endocrine therapy than with no treatment. CONCLUSIONS: Extremely elderly patients, especially those with Stages I and II breast cancer do not fare worse than younger patients, and should be offered surgery if they are fit.

Outcome after neoadjuvant chemotherapy in Asian breast cancer patients.

We aim to identify clinicopathologic predictors for response to neoadjuvant chemotherapy and to evaluate the prognostic value of pathologic complete response (pCR) on survival in Asia. This study included 915 breast cancer patients who underwent neoadjuvant chemotherapy at five public hospitals in Singapore and Malaysia. pCR following neoadjuvant chemotherapy was defined as 1) no residual invasive tumor cells in the breast (ypT0/is) and 2) no residual invasive tumor cells in the breast and axillary lymph nodes (ypT0/is ypN0). Association between pCR and clinicopathologic characteristics and treatment were evaluated using chi-square test and multivariable logistic regression. Kaplan-Meier analysis and log-rank test, stratified by other prognostic factors, were conducted to compare overall survival between patients who achieved pCR and patients who did not. Overall, 4.4% of nonmetastatic patients received neoadjuvant chemotherapy. The median age of preoperatively treated patients was 50 years. pCR rates were 18.1% (pCR ypT0/is) and 14.4% (pCR ypT0/is ypN0), respectively. pCR rate was the highest among women who had higher grade, smaller size, estrogen receptor negative, human epidermal growth factor receptor 2-positive disease or receiving taxane-based neoadjuvant chemotherapy. Patients who achieved pCR had better overall survival than those who did not. In subgroup analysis, the survival advantage was only significant among women with estrogen receptor-negative tumors. Patients with poor prognostic profile are more likely to achieve pCR and particularly when receiving taxane-containing chemotherapy. pCR is a significant prognostic factor for overall survival especially in estrogen receptor-negative breast cancers.

Trends in Post-Mastectomy Reconstruction in an Asian Population: A 12-Year Institutional Review.

Post-mastectomy breast reconstruction is an integral component of breast cancer treatment. It is often perceived that women in Asian countries have a lower rate of post-mastectomy reconstruction than Western populations. This study describes trends in timing and types of breast reconstruction performed in the largest healthcare provider in Singapore, over a period of 12 years. It also reports on the oncological outcomes and surgical safety. A retrospective review of all patients who underwent post-mastectomy reconstruction from January 2001 to December 2012 at the National Cancer Centre Singapore and Singapore General Hospital was performed. Six hundred and twenty post-mastectomy reconstructions were performed in 579 patients. The proportion of reconstructions increased from 4% in 2001 to 18% in 2012. Younger patients (<50 years old) and those with early stage cancer were more likely to undergo reconstruction. Immediate breast reconstruction was favored by more than 90% of patients. Postoperatively, 9% developed acute surgical complications that were treated surgically; 6% had additional surgery for late complications. Only 4% had delay of adjuvant chemotherapy. At median follow-up of 63 months (range 3-166), loco-regional recurrence was 4%, and distant metastases 8%. Post-mastectomy reconstruction for breast cancer is increasingly performed in our institution. Both younger age and lower stage disease were associated with choice for reconstruction in our study. Low rates of delay to adjuvant therapy were noted, and it may safely be offered to suitable women undergoing mastectomy.

Breast sarcomas and malignant phyllodes tumours: comparison of clinicopathological features, treatment strategies, prognostic factors and outcomes.

We aimed to compare the clinicopathological features, treatment strategies and clinical outcomes of breast sarcomas (BS) and malignant phyllodes tumours (MPT), and determine their prognostic factors. Cases of BS and MPT diagnosed at the Department of Pathology, Singapore General Hospital from January 1991 to December 2014 were derived from department files. Clinicopathological features, treatment strategies and survivals of patients with BS and MPT were compared. Prognostic indicators for BS and MPT were identified. BS and MPT were comparable in all except one of their clinicopathological features. A significantly higher proportion of BS patients had a history of previous breast carcinoma and thus radiation to the chest as compared to the MPT group (17.6 vs 0 %, P = 0.018). There was no significant difference in survival outcomes between BS and MPT. The 5-year disease-free survivals (DFS) for BS and MPT were 59.1 and 57.4 % respectively (P = 0.816), while the 5-year overall survivals (OS) for BS and MPT were 86.5 and 78.5 % respectively (P = 0.792). Combining both groups of tumours, univariate analysis showed that DFS was significantly affected by multifocality (P = 0.019), histological subtype (P = 0.014), presence of malignant heterologous elements (P < 0.001) and margin status (P = 0.023). Margin status was the only parameter which had a significant impact on OS (P = 0.040). Multivariate analysis confirmed the above findings. BS and MPT are rare entities with remarkable heterogeneity. They share similar clinicopathological features and outcomes, provoking thoughts on their biological relationship and clinical significance of pathologic distinction.