Can the size of chest wall recurrence after mastectomy in breast cancer patients predict the presence of systemic metastasis?

Background: One of the manifestations of recurrence after mastectomy is the presentation of chest wall lesion. However, it is unclear if the size of the chest wall recurrence (CWR) is related to the presence of simultaneous systemic metastasis in these patients. We aimed to determine if the size of the CWR could affect the outcome in these patients. Methods: Stage I-III breast cancer patients who underwent mastectomy and developed invasive ipsilateral CWR were included. Patients with bilateral mastectomy were excluded. Demographic, radiologic and pathological data were analysed between patients with CWR and simultaneous systemic metastasis versus those with isolated CWR. Results: Of the 1,619 patients treated with mastectomy, 214 (13.2%) patients developed recurrences. 57/214 (26.6%) patients had invasive ipsilateral CWR. 48 patients were analysed after exclusion of patients with missing data. Mean age at diagnosis of first cancer and at recurrence were 55.2 years (32-84 years) and 58.5 years (34-85 years) respectively. 26/48 (54.2%) had CWR with simultaneous systemic metastasis. Mean CWR size was 30.7 mm (6-121 mm) and 21.4 mm (5.3-90 mm) for the patients with simultaneous systemic metastasis and those without respectively (P=0.441). Grade (P=0.0008) and nodal status (P=0.0009) at primary diagnosis, grade (P=0.0011) and progesterone receptor (PR) status (P=0.0487) at recurrence were statistically significant for systemic metastasis in patients with CWR. Conclusions: Biologic factors such as grade of primary and recurrent cancer, PR status of recurrent cancer and nodal status at primary diagnosis, instead of CWR size, were associated with simultaneous systemic metastasis in patients with CWR.

Axillary management of breast cancer patients with isolated chest wall recurrence after mastectomy.

Background: National Comprehensive Cancer Network (NCCN) guidelines on the axillary management of breast cancer patients with isolated chest wall recurrence after mastectomy are unclear. Though sentinel lymph node biopsy (SLNB) is possible and may be considered, there is limited data on its usefulness. We aimed to determine if axillary restaging surgery was required in this cohort of patients who developed operable isolated chest wall recurrences after mastectomy. Methods: Breast cancer patients treated at a tertiary institution from 1st September 2005 to 31st October 2017 and developed isolated chest wall invasive recurrences after mastectomy were retrospectively reviewed. We excluded patients with bilateral cancers, concurrent regional or distant metastases, patients without surgery for their chest wall recurrences and patients who were lost to follow-up. The demographics, pathological data and second recurrences were collected from a prospectively maintained database and compared between patients with axillary lymph node dissection (ALND), SLNB and no axillary operation. Results: Of the 1,841 patients who underwent mastectomy, 26 (1.4%) patients developed isolated chest wall recurrences. Twenty two eligible patients were analysed. The mean age at diagnosis of the recurrence was 54.7 years (range, 37-84 years). 1, 2 and 19 patients had ALND, SLNB and no axillary operation respectively. On mean follow-up of 38.3 months, no axillary recurrences were noted. Conclusions: In breast cancer patients with isolated chest wall recurrences after mastectomy, axillary restaging surgery can be safely omitted with no increased axillary recurrences on medium term follow-up. This finding could refine existing guidelines in the management of the axilla for patients with chest wall recurrences after mastectomy.

Profiling Microbial Communities in Idiopathic Granulomatous Mastitis.

Idiopathic granulomatous mastitis (IGM) is a rare and benign inflammatory breast disease with ambiguous aetiology. Contrastingly, lactational mastitis (LM) is commonly diagnosed in breastfeeding women. To investigate IGM aetiology, we profiled the microbial flora of pus and skin in patients with IGM and LM. A total of 26 patients with IGM and 6 patients with LM were included in the study. The 16S rRNA sequencing libraries were constructed from 16S rRNA gene amplified from total DNA extracted from pus and skin swabs in patients with IGM and LM controls. Constructed libraries were multiplexed and paired-end sequenced on HiSeq4000. Metagenomic analysis was conducted using modified microbiome abundance analysis suite customised R-resource for paired pus and skin samples. Microbiome multivariable association analyses were performed using linear models. A total of 21 IGM and 3 LM paired pus and skin samples underwent metagenomic analysis. Bray−Curtis ecological dissimilarity distance showed dissimilarity across four sample types (IGM pus, IGM skin, LM pus, and LM skin; PERMANOVA, p < 0.001). No characteristic dominant genus was observed across the IGM samples. The IGM pus samples were more diverse than corresponding IGM skin samples (Shannon and Simpson index; Wilcoxon paired signed-rank tests, p = 0.022 and p = 0.07). Corynebacterium kroppenstedtii, reportedly associated with IGM in the literature, was higher in IGM pus samples than paired skin samples (Wilcoxon, p = 0.022). Three other species and nineteen genera were statistically significant in paired IGM pus−skin comparison after antibiotic treatment adjustment and multiple comparisons correction. Microbial profiles are unique between patients with IGM and LM. Inter-patient variability and polymicrobial IGM pus samples cannot implicate specific genus or species as an infectious cause for IGM.

Patterns of breast cancer second recurrences in patients after mastectomy.

INTRODUCTION: Little is known about second recurrences in breast cancer patients, especially in patients with mastectomy. We aimed to determine the risk factors, prevalence and patterns of second recurrence in mastectomy patients after first recurrence. METHODS: Stage I-III breast cancer patients treated at a tertiary institution from 1st September 2005 to 31st October 2017 and developed first and second recurrences after mastectomy were retrospectively reviewed. We excluded patients with bilateral cancers and patients who were lost to follow-up. The demographics, pathological and recurrence data were collected from a prospectively maintained database and analysed. RESULTS: Of the 1619 mastectomy patients, 214 (13.2%) patients developed recurrences at a mean 39.9 months from primary cancer diagnosis. 23, 8 and 183 had isolated chest wall recurrences (CWR), regional and systemic metastases, respectively. Excluding 2 CWR patients without surgery, second recurrences occurred in 3/21 (14.3%) and 3/8 (37.5%) in patients with CWR and regional metastasis at 27.7 months (range: 5-42) and 32 months (range: 18-40), respectively. In both groups, systemic metastasis as second recurrence occurred within 2 years after first recurrence, whilst locoregional second recurrences occurred later. No risk factors for second recurrence were identified. CONCLUSION: In patients with mastectomy, second recurrences occurred in 20.7% of patients with treated locoregional first recurrence, with no risk factors identified. Systemic metastases manifesting as second recurrence occurred in the first 2 years after first recurrence. Continued clinical surveillance and restaging patients in the first 2 years after first locoregional recurrence may enable early prognostication and treatment with the newer metastatic drugs.

Association between Breast Cancer Polygenic Risk Score and Chemotherapy-Induced Febrile Neutropenia: Null Results.

BACKGROUND: The hypothesis that breast cancer (BC) susceptibility variants are linked to chemotherapy-induced toxicity has been previously explored. Here, we investigated the association between a validated 313-marker-based BC polygenic risk score (PRS) and chemotherapy-induced neutropenia without fever and febrile neutropenia (FNc) in Asian BC patients. METHODS: This observational case-control study of Asian BC patients treated with chemotherapy included 161 FNc patients, 219 neutropenia patients, and 936 patients who did not develop neutropenia. A continuous PRS was calculated by summing weighted risk alleles associated with overall, estrogen receptor- (ER-) positive, and ER-negative BC risk. PRS distributions neutropenia or FNc cases were compared to controls who did not develop neutropenia using two-sample t-tests. Odds ratios (OR) and corresponding 95% confidence intervals were estimated for the associations between PRS (quartiles and per standard deviation (SD) increase) and neutropenia-related outcomes compared to controls. RESULTS: PRS distributions were not significantly different in any of the comparisons. Higher PRSoverall quartiles were negatively correlated with neutropenia or FNc. However, the associations were not statistically significant (PRS per SD increase OR neutropenia: 0.91 [0.79-1.06]; FNc: 0.87 [0.73-1.03]). No dose-dependent trend was observed for the ER-positive weighted PRS (PRSER-pos) and ER-negative weighted PRS (PRSER-neg). CONCLUSION: BC PRS was not strongly associated with chemotherapy-induced neutropenia or FNc.

Impact of Subsidy on the Use of Personalized Medicine in Breast Cancer.

OBJECTIVES: Advances in adjuvant therapy have led to increased survival rates after cancer prognosis. Herceptin, a targeted therapy, had first been introduced to Singapore in 2006. We aimed to assess whether subsidies for Herceptin from 2012 will lead to changes in uptake among HER2-positive patients by socioeconomic groups. METHODS: Random-intercept logistic regression was used to model diagnostic test and Herceptin uptake using the Singapore Breast Cancer Cohort from 2006 to 2018, adjusting for covariates such as education, housing type, and marital status before and after subsidies. Interrupted time series analysis was used to evaluate the impact of Herceptin subsidy on treatment uptake. Concentration index was also computed by ethnicity and education to measure inequality in uptake. RESULTS: We found that the odds of diagnostic testing were not associated with socioeconomic factors. Nevertheless, before subsidies, highest education attained (odds ratio 4.57; 95% confidence interval 1.90-11.02; P<.01) significantly increased the odds of Herceptin uptake. These odds were leveled after the introduction of subsidies to Herceptin treatment from 2012. After subsidy, we also found that Herceptin uptake increased significantly by 11.4% (95% confidence interval 3.47-19.4; P=.016). In addition, inequality of Herceptin use decreased especially among the Indians, where at least 40% were used in the higher educated group before subsidy. CONCLUSIONS: Subsidies have lowered the barriers to Herceptin uptake for marginalized individuals. Having targeted subsidies for socioeconomically disadvantaged groups may work more efficiently in providing ease of access than a blanket subsidy in Herceptin.

Predicting the Likelihood of Carrying a BRCA1 or BRCA2 Mutation in Asian Patients With Breast Cancer.

PURPOSE: With the development of poly (ADP-ribose) polymerase inhibitors for treatment of patients with cancer with an altered BRCA1 or BRCA2 gene, there is an urgent need to ensure that there are appropriate strategies for identifying mutation carriers while balancing the increased demand for and cost of cancer genetics services. To date, the majority of mutation prediction tools have been developed in women of European descent where the age and cancer-subtype distributions are different from that in Asian women. METHODS: In this study, we built a new model (Asian Risk Calculator) for estimating the likelihood of carrying a pathogenic variant in BRCA1 or BRCA2 gene, using germline BRCA genetic testing results in a cross-sectional population-based study of 8,162 Asian patients with breast cancer. We compared the model performance to existing mutation prediction models. The models were evaluated for discrimination and calibration. RESULTS: Asian Risk Calculator included age of diagnosis, ethnicity, bilateral breast cancer, tumor biomarkers, and family history of breast cancer or ovarian cancer as predictors. The inclusion of tumor grade improved significantly the model performance. The full model was calibrated (Hosmer-Lemeshow P value = .614) and discriminated well between BRCA and non-BRCA pathogenic variant carriers (area under receiver operating curve, 0.80; 95% CI, 0.75 to 0.84). Addition of grade to the existing clinical genetic testing criteria targeting patients with breast cancer age younger than 45 years reduced the proportion of patients referred for genetic counseling and testing from 37% to 33% (P value = .003), thereby improving the overall efficacy. CONCLUSION: Population-specific customization of mutation prediction models and clinical genetic testing criteria improved the accuracy of BRCA mutation prediction in Asian patients.

Characterisation of protein-truncating and missense variants in PALB2 in 15 768 women from Malaysia and Singapore.

BACKGROUND: Rare protein-truncating variants (PTVs) in partner and localiser of BRCA2 (PALB2) confer increased risk to breast cancer, but relatively few studies have reported the prevalence in South-East Asian populations. Here, we describe the prevalence of rare variants in PALB2 in a population-based study of 7840 breast cancer cases and 7928 healthy Chinese, Malay and Indian women from Malaysia and Singapore, and describe the functional impact of germline missense variants identified in this population. METHODS: Mutation testing was performed on germline DNA (n=15 768) using targeted sequencing panels. The functional impact of missense variants was tested in mouse embryonic stem cell based functional assays. RESULTS: PTVs in PALB2 were found in 0.73% of breast cancer patients and 0.14% of healthy individuals (OR=5.44; 95% CI 2.85 to 10.39, p<0.0001). In contrast, rare missense variants in PALB2 were not associated with increased risk of breast cancer. Whereas PTVs were associated with later stage of presentation and higher-grade tumours, no significant association was observed with missense variants in PALB2. However, two novel rare missense variants (p.L1027R and p.G1043V) produced unstable proteins and resulted in a decrease in homologous recombination-mediated repair of DNA double-strand breaks. CONCLUSION: Despite genetic and lifestyle differences between Asian and other populations, the population prevalence of PALB2 PTVs and associated relative risk of breast cancer, are similar to those reported in European populations.

Polygenic risk scores for prediction of breast cancer risk in Asian populations.

PURPOSE: Non-European populations are under-represented in genetics studies, hindering clinical implementation of breast cancer polygenic risk scores (PRSs). We aimed to develop PRSs using the largest available studies of Asian ancestry and to assess the transferability of PRS across ethnic subgroups. METHODS: The development data set comprised 138,309 women from 17 case-control studies. PRSs were generated using a clumping and thresholding method, lasso penalized regression, an Empirical Bayes approach, a Bayesian polygenic prediction approach, or linear combinations of multiple PRSs. These PRSs were evaluated in 89,898 women from 3 prospective studies (1592 incident cases). RESULTS: The best performing PRS (genome-wide set of single-nucleotide variations [formerly single-nucleotide polymorphism]) had a hazard ratio per unit SD of 1.62 (95% CI = 1.46-1.80) and an area under the receiver operating curve of 0.635 (95% CI = 0.622-0.649). Combined Asian and European PRSs (333 single-nucleotide variations) had a hazard ratio per SD of 1.53 (95% CI = 1.37-1.71) and an area under the receiver operating curve of 0.621 (95% CI = 0.608-0.635). The distribution of the latter PRS was different across ethnic subgroups, confirming the importance of population-specific calibration for valid estimation of breast cancer risk. CONCLUSION: PRSs developed in this study, from association data from multiple ancestries, can enhance risk stratification for women of Asian ancestry.

Germline breast cancer susceptibility genes, tumor characteristics, and survival.

BACKGROUND: Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent. METHODS: Gene panel sequencing was performed for 34 known or suspected breast cancer predisposition genes, of which nine genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, and TP53) were associated with breast cancer risk. Associations between PTV carriership in one or more genes and tumor characteristics were examined using multinomial logistic regression. Ten-year overall survival was estimated using Cox regression models in 6477 breast cancer patients after excluding older patients (≥75years) and stage 0 and IV disease. RESULTS: PTV9genes carriership (n = 690) was significantly associated (p < 0.001) with more aggressive tumor characteristics including high grade (poorly vs well-differentiated, odds ratio [95% confidence interval] 3.48 [2.35-5.17], moderately vs well-differentiated 2.33 [1.56-3.49]), as well as luminal B [HER-] and triple-negative subtypes (vs luminal A 2.15 [1.58-2.92] and 2.85 [2.17-3.73], respectively), adjusted for age at diagnosis, study, and ethnicity. Associations with grade and luminal B [HER2-] subtype remained significant after excluding BRCA1/2 carriers. PTV25genes carriership (n = 289, excluding carriers of the nine genes associated with breast cancer) was not associated with tumor characteristics. However, PTV25genes carriership, but not PTV9genes carriership, was suggested to be associated with worse 10-year overall survival (hazard ratio [CI] 1.63 [1.16-2.28]). CONCLUSIONS: PTV9genes carriership is associated with more aggressive tumors. Variants in other genes might be associated with the survival of breast cancer patients. The finding that PTV carriership is not just associated with higher breast cancer risk, but also more severe and fatal forms of the disease, suggests that genetic testing has the potential to provide additional health information and help healthy individuals make screening decisions.

Outcomes of Stage I and II Breast Cancer with Nodal Micrometastases Treated with Mastectomy without Axillary Therapy.

PURPOSE: Studies that report equivalent oncologic outcomes of sentinel lymph node biopsy (SLNB) alone versus axillary lymph node dissection (ALND) for T1-2N1mi breast cancers are heavily weighted with patients who received breast-conserving surgery (BCS). The impact of omitting ALND in N1mi patients treated with mastectomy is not well studied. It is also unknown if these patients would benefit from post-mastectomy radiotherapy (PMRT). This study reports the outcomes of patients with T1-2N1mi breast cancer treated by mastectomy without axillary therapy. METHODS: Patients who had T1-2N1mi breast cancer and underwent mastectomy from January 1998 to December 2018 were identified from our multi-institutional prospective database. Axillary recurrence rate (ARR), disease-free survival (DFS), and overall survival (OS) are reported. RESULTS: 260 patients with pT1-2N1mi breast cancer who had mastectomy were identified. They had either SLNB (35.4%) or ALND (64.6%). Majority of these patients received adjuvant systemic therapy (93.8%). 77 (29.6%) patients received radiotherapy, 31 after SLNB and 46 after ALND. At median follow-up of 61 months, ARR was 1.1% (n = 1) in the SLNB only group, vs. 0.6% (n = 1) in the ALND group (p = 0.752). DFS and OS were not significantly different between patients with SLNB alone versus ALND (p = 0.40 and p = 0.27, respectively). Among 92 patients who had SLNB only, no DFS or OS difference was observed with the use of PMRT. CONCLUSION: In T1-2N1mi patients with mastectomy and SLNB, axillary recurrences were rare. No statistically significant differences were noted between patients with SLNB, ALND, or PMRT. Our findings suggest that these patients may be safely treated without axillary therapy.

Effects of housing value and medical subsidy on treatment and outcomes of breast cancer patients in Singapore: A retrospective cohort study.

BACKGROUND: Socioeconomic status (SES) is likely to affect survival in breast cancer patients. Housing value is a reasonable surrogate for SES in Singapore where most residents own their own homes, which could be public (subsidised) or private housing. We evaluated effects of housing value and enhanced medical subsidies on patients' presentation, treatment choices, compliance and survival in a setting of good access to healthcare. METHODS: A retrospective analysis of breast cancer patients treated in a tertiary hospital cluster from 2000 to 2016 was performed. Individual-level Housing value Index (HI) was derived from each patient's address and then grouped into 3 tiers: HI(high)(minimal subsidy), HI(med)(medium subsidy) and HI(low)(high subsidy). Cox regression was performed to evaluate the associations between overall survival (OS) and cancer-specific survival (CSS) with HI and various factors. FINDINGS: We studied a multiracial cohort of 15,532 Stage 0-IV breast cancer patients. Median age was 53.7 years and median follow-up was 7.7 years. Patients with lower HI presented with more advanced disease and had lower treatment compliance. On multivariable analysis, compared to HI(high) patients, HI(med) patients had decreased OS (HR=1.14, 95% CI 1.05-1.23) and CSS (HR=1.15, 95% CI 1.03-1.27), and HI(low) patients demonstrated reduced OS (HR=1.16, 95% CI 1.01-1.33). Ten-year non-cancer mortality was higher in lower HI-strata. Enhanced medical subsidy approximately halved treatment noncompliance rates but its receipt was not an independent prognostic factor for survival. INTERPRETATION: Despite good healthcare access, lower-HI patients have poorer survival from both cancer and non-cancer causes, possibly due to delayed health-seeking and poorer treatment compliance. Enhanced subsidies may mitigate socioeconomic disadvantages. FUNDING: None.

Cohort profile: The Singapore Breast Cancer Cohort (SGBCC), a multi-center breast cancer cohort for evaluation of phenotypic risk factors and genetic markers.

This article aims to provide a detailed description of the Singapore Breast Cancer Cohort (SGBCC), an ongoing multi-ethnic cohort established with the overarching goal to identify genetic markers for breast cancer risk, prognosis and treatment response, as well as to understand the ethnic differences in disease risk and outcome in an Asian setting. The cohort comprises of breast cancer patients aged 21 years and above from six public hospitals which diagnose and treat nearly 76% breast cancer cases in Singapore. Self-reported data on sociodemographic and lifestyle, reproductive risk factors, medical history and family history of breast or ovarian cancer is collected using a structured questionnaire. Clinical data on tumour characteristics, and treatment modalities are obtained through medical record. Bio-specimens (blood or saliva) is collected at recruitment. Follow-up on survival information is done through routine linkage with the Registry of Births and Deaths. As of 31 December 2016, 7,768 subjects have been recruited to the study with 76% subjects contributed bio-specimens. The SGBCC provides a valuable platform which offers a unique, large and rich resource for new research ideas on breast cancer related phenotypic risk factors and genetic markers.

DNA methylation and breast cancer-associated variants.

BACKGROUND: A breast cancer polygenic risk score (PRS) comprising 313 common variants reliably predicts disease risk. We examined possible relationships between genetic variation, regulation, and expression to clarify the molecular alterations associated with these variants. METHODS: Genome-wide methylomic variation was quantified (MethylationEPIC) in Asian breast cancer patients (1152 buffy coats from peripheral whole blood). DNA methylation (DNAm) quantitative trait loci (mQTL) mapping was performed for 235 of the 313 variants with minor allele frequencies > 5%. Stability of identified mQTLs (p < 5e-8) across lifetime was examined using a public mQTL database. Identified mQTLs were also mapped to expression quantitative trait loci (eQTLs) in the Genotype-Tissue Expression Project and the eQTLGen Consortium. RESULTS: Breast cancer PRS was not associated with DNAm. A higher proportion of significant cis-mQTLs were observed. Of 822 significant cis-mQTLs (179 unique variants) identified in our dataset, 141 (59 unique variants) were significant (p < 5e-8) in a public mQTL database. Eighty-six percent (121/141) of the matched mQTLs were consistent at multiple time points (birth, childhood, adolescence, pregnancy, middle age, post-diagnosis, or treatment). Ninety-three variants associated with DNAm were also cis-eQTLs (35 variants not genome-wide significant). Multiple loci in the breast cancer PRS are associated with DNAm, contributing to the polygenic nature of the disease. These mQTLs are mostly stable over time. CONCLUSIONS: Consistent results from DNAm and expression data may reveal new candidate genes not previously associated with breast cancer.

European polygenic risk score for prediction of breast cancer shows similar performance in Asian women.

Polygenic risk scores (PRS) have been shown to predict breast cancer risk in European women, but their utility in Asian women is unclear. Here we evaluate the best performing PRSs for European-ancestry women using data from 17,262 breast cancer cases and 17,695 controls of Asian ancestry from 13 case-control studies, and 10,255 Chinese women from a prospective cohort (413 incident breast cancers). Compared to women in the middle quintile of the risk distribution, women in the highest 1% of PRS distribution have a ~2.7-fold risk and women in the lowest 1% of PRS distribution has ~0.4-fold risk of developing breast cancer. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. A PRS developed for European-ancestry women is also predictive of breast cancer risk in Asian women and can help in developing risk-stratified screening programmes in Asia.

Human epidermal growth factor receptor 2 positive rates in invasive lobular breast carcinoma: The Singapore experience.

BACKGROUND: Invasive lobular carcinomas (ILC) form 5%-10% of breast cancer and rarely show overexpression of human epidermal growth factor receptor 2 (HER2). AIM: To describe the prevalence and prognostic factors of HER2 positive (HER2+) ILC in an Asian population. METHODS: A retrospective review of patients with ILC seen between January 1985 and March 2018 at various SingHealth medical institutions was conducted. Demographic and clinical data were collected from medical records. We examined clinicopathological characteristics and survival in relation to HER2 status. RESULTS: A total of 864 patients were included. Prevalence of HER2 positivity was 10.1% (87 patients). Compared with HER2 negative (HER2-) ILC, HER2+ ILC was associated with a higher proportion of estrogen receptor negative (24.4% vs 5.9%, P < 0.001), progesterone receptor negative (PR-) (40.2% vs 24%, P = 0.002) and grade 3 tumours (Grade 3, 29.0% vs 10.2%, P < 0.001). Overall survival rate was poorer in patients with HER2+ compared to HER2- ILC (56.7% vs 72.9% alive at 10 years; hazard ratio 1.87, 95% confidence interval: 1.21-2.90, P = 0.004). Based on multivariate analysis, negative prognostic factors for overall survival included HER2 positivity, PR negativity, older age, Indian ethnicity and higher tumour stage. CONCLUSION: Prevalence of HER2+ ILC was 10.1%. HER2+ ILC was more likely to have poorer prognostic features such as estrogen receptor negative, PR- and higher tumour grade, and have a poorer survival.

Impact of deviation from guideline recommended treatment on breast cancer survival in Asia.

Breast cancer survival has improved with significant progress in treatment and disease management. However, compliance with treatment varies. Treatment guidelines for older patients are unclear. We aim to identify predictors of noncompliance with recommended therapy in a large breast cancer population and assess the impact of noncompliance on survival. Our study included 19,241 non-metastatic female breast cancer patients, of whom 3,158 (16%) died within 10 years post-diagnosis (median survival = 5.8 years). We studied the association between treatment noncompliance and factors with logistic regression, and the impact of treatment noncompliance on survival with a flexible parametric survival model framework. The highest proportion of noncompliance was observed for chemotherapy (18%). Predictors of noncompliance with chemotherapy, radiotherapy and endocrine therapy included age, tumor size, nodal involvement and subtype (except radiotherapy). Factors associated with not receiving surgery included age and subtype. Treatment noncompliance was associated with worse overall survival for surgery (HR: 2.26 [1.80-2.83]), chemotherapy (1.25 [1.11-1.41]), radiotherapy (2.28 [1.94-2.69]) and endocrine therapy (1.70 [1.41-2.04]). Worse survival was similarly observed in older patients for whom guidelines generally do not apply. Our results highlight the importance of following appropriate treatment as recommended by current guidelines. Older patients may benefit from similar recommendations.

Patterns of relapse after neoadjuvant chemotherapy in breast cancer: implications for surveillance in clinical practice.

PURPOSE: This study aimed to identify patterns of relapse after neoadjuvant chemotherapy (NAC) for breast cancer to refine follow-up recommendations. METHODS: Retrospective analysis on 523 breast cancer patients treated with NAC at two public hospitals in Singapore between 2000 and 2014. RESULTS: Majority of patients (71.9%) had locally advanced disease. Median follow-up was 55 months. 5-year recurrence rate was significantly higher in triple negative breast cancer (TNBC) than non-TNBC subtypes (38.4% vs. 29.5%; p = 0.042); 85% of recurrences involved distant sites. Among TNBC and HR (hormone receptor)-/HER2+ subtypes, 97.0% and 95.0% of relapses occurred within 3 years from diagnosis respectively while 10.6% of relapses among HR+ subgroup occurred beyond 5 years. Recurrence risk in high-grade tumours decreased with time. Stage III at diagnosis (hazard ratio = 2.94; p < 0.001), grade 3 tumours (hazard ratio = 2.87; p = 0.018), not achieving pathologic complete response (pCR) (hazard ratio = 8.77; p = 0.003) and not receiving adjuvant radiotherapy (hazard ratio = 3.19; p < 0.001) were independent predictors of inferior recurrence-free survival. Serum CA 15-3 was raised in 49% of patients upon relapse; it correlated with inferior post-relapse survival (median 11 months vs. 22 months; p = 0.019). CONCLUSIONS: While more intensive follow-up during the first 3 years may be required for patients who do not achieve pCR, especially those with TNBC and HR-/HER2+ tumours, the benefit from blood tests such as CA 15-3 appears limited, and the benefit from intensification of surveillance remains to be addressed in prospective studies on high-risk patients.

Granulomatous Mastitis and Factors Associated with Recurrence: An 11-Year Single-Centre Study of 113 Patients in Singapore.

BACKGROUND: Granulomatous mastitis (GM) is an inflammatory breast disease of unknown aetiology. It poses diagnostic and therapeutic challenges with myriad forms of clinical presentation, varying results to treatments and propensity to recur. This study aims to look at clinical and treatment factors that predispose to recurrence of GM. METHODS: We performed a retrospective review of 113 patients in our unit with histologically proven GM from 2006 to 2016. Demographic, clinical, treatment and outcomes data were collected and analysed. RESULTS: Eighty-nine patients were treated with antibiotics (78.8%), 79 (69.9%) with steroids and 23 (20.4%) patients underwent surgery. Twenty (17.7%) patients had recurrence. Patients who presented with inflammatory signs and symptoms had increased odds of having subsequent recurrence: skin changes (1.50), pain (2.00), fistula (4.39) and antibiotic treatment (6.65). Four patients (20%) with recurrence had positive bacterial cultures. All 4 grew Corynebacterium. Patients with Corynebacterium infection had a 2.64 times higher risk of recurrence. Surgery did not preclude recurrence. There was a 70% (7/10) penicillin resistance rate in our patients with positive cultures for Corynebacterium. CONCLUSION: Initial presentation with inflammatory signs and symptoms may confer increased risk of recurrence, warranting closer monitoring. Corynebacterium infection may play a part as a causative factor and risk factor for recurrence. Non-penicillin antibiotics should be considered as first-line antibiotics for patients presenting with inflammatory changes. Further prospective studies with larger patient populations might reveal information on the aetiology of GM and result in the development of a more standardized and effective treatment regimen.