A radiomic model to classify response to neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Medical image analysis has evolved to facilitate the development of methods for high-throughput extraction of quantitative features that can potentially contribute to the diagnostic and treatment paradigm of cancer. There is a need for further improvement in the accuracy of predictive markers of response to neo-adjuvant chemotherapy (NAC). The aim of this study was to develop a radiomic classifier to enhance current approaches to predicting the response to NAC breast cancer. METHODS: Data on patients treated for breast cancer with NAC prior to surgery who had a pre-NAC dynamic contrast enhanced breast MRI were included. Response to NAC was assessed using the Miller-Payne system on the excised tumor. Tumor segmentation was carried out manually under the supervision of a consultant breast radiologist. Features were selected using least absolute shrinkage selection operator regression. A support vector machine learning model was used to classify response to NAC. RESULTS: 74 patients were included. Patients were classified as having a poor response to NAC (reduction in cellularity < 90%, n = 44) and an excellent response (> 90% reduction in cellularity, n = 30). 4 radiomics features (discretized kurtosis, NGDLM contrast, GLZLM_SZE and GLZLM_ZP) were identified as pertinent predictors of response to NAC. A SVM model using these features stratified patients into poor and excellent response groups producing an AUC of 0.75. Addition of estrogen receptor status improved the accuracy of the model with an AUC of 0.811. CONCLUSION: This study identified a radiomic classifier incorporating 4 radiomics features to augment subtype based classification of response to NAC in breast cancer.

Clinicopathological correlates, oncological impact, and validation of Oncotype DX™ in a European Tertiary Referral Centre.

Oncotype DX™ (ODX) score estimates prognosis and predicts breast cancer recurrence. It also individualizes patient adjuvant chemotherapy prescription in breast cancer. This assay relies on genetic and molecular markers; the clinicopathological phenotype of which are tested routinely. The aim of this study was determine whether clinicopathological and immunohistochemical information predicts ODX recurrence score (RS). Secondly, to assess the impact on adjuvant chemotherapy (AC) and oncological outcome of ODX testing in patients in a European tertiary referral center. Estrogen receptor positive (ER+), human epidermal growth factor receptor-2 negative (HER2-), lymph node negative (LN-), and female breast cancer patients with ODX testing performed between 2007 and 2015 were categorized into low- (<11), intermediate- (11-25), and high-risk (>25) groups. Clinicopathological and immunohistochemical correlates of RS were determined. Predictors of RS were assessed using binary logistic regression. Oncological outcome was assessed using Kaplan-Meier and Cox regression analyses. ODX was performed in 400 consecutive ER+LN- patients. Median follow-up was 74.1 months (3.0-144.4). Low grade (odds ratio [OR]:2.39; 95% confidence interval [CI]:1.04-5.51, p = 0.041) independently predicted low ODX, while high grade (OR:2.04; 95% CI: 1.19-3.49, p = 0.009) and reduced progesterone receptor (PgR) expression (OR: 2.57, 95% CI: 1.42-4.65, p = 0.002) independently predicted high ODX. Omission of AC in intermediate- (p = 0.159) and high-risk (p = 0.702) groups did not negatively impact survival. In conclusion, tumor grade independently predicts low and high RS, while PgR negativity predicts high RS. ODX reduced AC prescription without compromising oncological outcome.

The histopathological and molecular features of breast carcinoma with tumour budding-a systematic review and meta-analysis.

PURPOSE: Tumour budding (TB) is an adverse histological feature in many epithelial cancers. It is thought to represent epithelial-mesenchymal transition, a key step in the metastatic process. The significance of TB in breast carcinoma (BC) remains unclear. The aim of this study is to investigate the relationship between TB and other histological and molecular features of BC. METHODS: A systematic search was performed to identify studies that compared features of BC based on the presence or absence of high-grade TB. Dichotomous variables were pooled as odds ratios (OR) using the Der Simonian-Laird method. Quality assessment of the included studies was performed using the Newcastle-Ottawa scale (NOS). RESULTS: Seven studies with a total of 1040 patients (high-grade TB n = 519, 49.9%; low-grade/absent TB n = 521, 50.1%) were included. A moderate to high risk of bias was noted. The median NOS was 7 (range 6-8). High-grade TB was significantly associated with lymph node metastasis (OR 2.32, 95% c.i. 1.77 to 3.03, P < 0.001) and lymphovascular invasion (OR 3.08, 95% c.i. 2.13 to 4.47, P < 0.001). With regard to molecular subtypes, there was an increased likelihood of high-grade TB in oestrogen (OR 1.66, 95% c.i. 1.21 to 2.29, P = 0.002) and progesterone receptor-positive (OR 1.48, 95% c.i. 1.09 to 2.02, P = 0.01) tumours. In contrast, triple-negative breast cancer had a reduced incidence of high-grade TB (OR 0.46, 95% c.i. 0.30 to 0.72, P = 0.0006). CONCLUSION: High-grade TB is enriched in hormone receptor-positive BC and is associated with known adverse prognostic variables. TB may offer new insights into the metastatic process of BC.

Science or popular media: What drives breast cancer online activity?

Google Trends is reflective of international awareness. Since its launch in 2004, there have been several landmark publications, international awareness campaigns, and mainstream-media events that involve breast cancer. The aim of this study was to assess the impact of landmark academic publications vs mainstream-media announcements in driving online breast cancer activity via Google Trends. Ten breast cancer-related themes or landmark publications (five academic publications and five media-related events) were used to compare the impact of online search activity. This activity was determined by retrospectively analyzing Google Trends data over a 12-year period (2004-2016) and calculating the relative search volume. Breast cancer searches showed a slight decrease in the twelve-year period. Since 2004, eight of top 10 Breast Cancer searches were in October. This coincides with breast cancer awareness month. The major five academic publications were all published in the New England Journal of Medicine or the Lancet. Interestingly, only one publication (Tailor-X trial) made the top 10 spikes in relative search volume. Academic publications as expected generate lower rates of public awareness and Internet searching. However, if academic publications are coupled with media releases, there is considerable potential for achieving increased public awareness.

Thoracic paravertebral blockade in breast surgery: Is pneumothorax an appreciable concern? A review of over 1000 cases.

There has been a substantial increase in ambulatory day-case breast surgery in recent decades. This has been largely due to improvements in anesthetic procedures and pre-emptive analgesia. Thoracic paravertebral blockade (TPVB) is increasing in popularity, though concerns over iatrogenic injury remain, especially pneumothorax. The purpose of this study was to conduct a review of the incidence of pneumothorax following TPVB prior to breast surgery. Data from of a consecutive series of patients having TPVB prior to breast surgery between 2009 and 2014 were reviewed. TPVB were used prior to unilateral and bilateral procedures. Medical records were retrospectively assessed for any complication including pleural punctures, pneumothorax, hypotension, bradycardia as well as signs and symptoms of local anesthetic toxicity. 1152 patients underwent a total of 1322 TPVB injections (982 unilateral and 340 bilateral). Clinically significant hypotension and/or bradycardia occurred in 26 patients (2.2%). Two patients (0.17%) had a suspected toxicity from the local anesthetic. Incidence of pleural puncture was 0.6% (n=9) and pneumothorax 0.26% (n=3). All pneumothoraxes were managed conservatively. There was no statistical difference in complication rates in those that had unilateral vs bilateral TPVB or those that had ultrasound guidance (P=.09). Good pre-emptive analgesia is pertinent to prevent acute postoperative pain. TPVB have been shown to be successful in reducing rescue analgesia. This study shows TPVB is a well-tolerated procedure, with a low associated incidence of iatrogenic injury and complication.

Locoregional Recurrence Following Breast Cancer Surgery in the Trastuzumab Era: A Systematic Review by Subtype.

INTRODUCTION: Increasing evidence suggests that molecular subtype influences locoregional recurrence (LRR) of breast cancer. Previous systematic reviews that evaluated the quantitative influence of subtype on LRR predated the use of Trastuzumab. This study assessed the impact of subtype on LRR in a contemporary treatment era. METHODS: A comprehensive search for all published studies assessing LRR according to breast cancer subtype was performed. Only studies with patients treated with Trastuzumab were included. Relevant data were extracted from each study for systematic review. Primary outcome was LRR related to breast cancer subtype. RESULTS: In total, 11,219 patients were identified from seven studies. Overall LRR rate was 3.44%. The lowest LRR rates were in luminal A (1.7%), and the highest rates were in triple-negative (7.4%) subtypes. There were significantly lower risks of LRR in patients with luminal A subtype compared with luminal B [odds ratio (OR) 0.54, 95% confidence interval (CI) 0.38-0.76; p < 0.0004], HER2/neu-overexpressing (OR 0.32, 95% CI 0.24-0.45; p < 0.0001) and triple-negative breast cancers (OR 0.25, 95% CI 0.19-0.32; p < 0.0001). There were significant differences in LRR between the luminal B and HER2/neu-overexpressing breast cancers (OR 0.61, 95% CI 0.41-0.89; p = 0.0145). The reduced risk in HER2/neu overexpressing compared with triple-negative breast cancers approached statistical significance (OR 0.75, 95% CI 0.55-1.03; p = 0.0933). CONCLUSIONS: Significant variations in LRR occur across breast cancer subtypes, with lowest rates in luminal cancers and highest rates in triple-negative breast cancers. Low levels of LRR highlight advances in breast cancer management in the contemporary era.

Exploring circulating micro-RNA in the neoadjuvant treatment of breast cancer.

Breast cancer is the most frequently diagnosed malignancy amongst females worldwide. In recent years the management of this disease has transformed considerably, including the administration of chemotherapy in the neoadjuvant setting. Aside from increasing rates of breast conserving surgery and enabling surgery via tumour burden reduction, use of chemotherapy in the neoadjuvant setting allows monitoring of in vivo tumour response to chemotherapeutics. Currently, there is no effective means of identifying chemotherapeutic responders from non-responders. Whilst some patients achieve complete pathological response (pCR) to chemotherapy, a good prognostic index, a proportion of patients derive little or no benefit, being exposed to the deleterious effects of systemic treatment without any knowledge of whether they will receive benefit. The identification of predictive and prognostic biomarkers could confer multiple benefits in this setting, specifically the individualization of breast cancer management and more effective administration of chemotherapeutics. In addition, biomarkers could potentially expedite the identification of novel chemotherapeutic agents or increase their efficacy. Micro-RNAs (miRNAs) are small non-coding RNA molecules. With their tissue-specific expression, correlation with clinicopathological prognostic indices and known dysregulation in breast cancer, miRNAs have quickly become an important avenue in the search for novel breast cancer biomarkers. We provide a brief history of breast cancer chemotherapeutics and explore the emerging field of circulating (blood-borne) miRNAs as breast cancer biomarkers for the neoadjuvant treatment of breast cancer. Established molecular markers of breast cancer are outlined, while the potential role of circulating miRNAs as chemotherapeutic response predictors, prognosticators or potential therapeutic targets is discussed.

Predicting general and cancer-related distress in women with newly diagnosed breast cancer.

BACKGROUND: Psychological distress can impact medical outcomes such as recovery from surgery and experience of side effects during treatment. Identifying the factors that explain variability in distress would guide future interventions aimed at decreasing distress. Two factors that have been implicated in distress are illness perceptions and coping, and are part of the Self-Regulatory Model of Illness Behaviour (SRM). The model suggests that coping mediates the relationship between illness perceptions and distress. Despite this; very little research has assessed this relationship with cancer-related distress, and none have examined women with screen-detected breast cancer. This study is the first to examine the relative contribution of illness perceptions and coping on general and cancer-related distress in women with screen-detected breast cancer. METHODS: Women recently diagnosed with breast cancer (N = 94) who had yet to receive treatment completed measures of illness perceptions (Revised Illness Perception Questionnaire), cancer-specific coping (Mental Adjustment to Cancer Scale), general anxiety and depression (Hospital Anxiety and Depression scale), and cancer-related distress. RESULTS: Hierarchical regression analyses revealed that medical variables, illness perceptions and coping predicted 50% of the variance in depression, 42% in general anxiety, and 40% in cancer-related distress. Believing in more emotional causes to breast cancer (ß = .22, p = .021), more illness identity (ß = .25, p = .004), greater anxious preoccupation (ß = .23, p = .030), and less fighting spirit (ß = -.31, p = .001) predicted greater depression. Greater illness coherence predicted less cancer-related distress (ß = -.20, p = .043). Greater anxious preoccupation also led to greater general anxiety (ß = .44, p < .001) and cancer-related distress (ß = .37, p = .001). Mediation analyses revealed that holding greater beliefs in a chronic timeline, more severe consequences, greater illness identity and less illness coherence increases cancer-specific distress (ps < .001) only if women were also more anxiously preoccupied with their diagnosis. CONCLUSIONS: Screening women for anxious preoccupation may help identify women with screen-detected breast cancer at risk of experiencing high levels of cancer-related distress; whilst illness perceptions and coping could be targeted for use in future interventions to reduce distress.

A genetic variant at 12p11 significantly modifies breast cancer risk in a genetically homogenous island population.

Genome-wide association studies have identified novel breast cancer susceptibility loci at 12q24 (rs1292011), 12p11 (rs10771399) and 21q21 (rs2823093). The aim of our study was to investigate the prevalence of variants at these three loci in an Irish sample, and to examine the association between these variants and breast cancer in this cohort. DNA was extracted from the blood or buccal swabs of Irish patients with breast cancer (cases), as well as from healthy Irish female controls. Genotyping was performed for each target using a Taqman-based platform. Data were analysed using IBM Statistical Package for the Social Sciences version 22. Genotyping was performed on samples from 1,267 patients with breast cancer and 841 cancer-free controls. The per-allele odds ratio associated with the minor allele at 12p11 was found to be 0.67 (0.54-0.81, p < 0.001). Genotype-specific odds ratios showed an allele dosage effect with odds ratio of 0.76 (0.6-0.95) for heterozygotes, and 0.23 (0.1-0.51) for rare homozygotes. Minor allele frequencies of the variants at 12q24 and 21q21 did not differ significantly between cases or controls. All three investigated variants were identified in the Irish population. The polymorphism rs10771399 was strongly associated with breast cancer risk in this cohort, and was shown to be associated with reduced odds ratio for all molecular subtypes.

Pre-emptive paracetamol reduces intra-operative opioid use in patients undergoing day-case oncologic breast surgery.

Minimization of intra-operative opioid use is an area of ongoing research interest with several potential benefits to the patient. Pre-emptive analgesia, defined as the administration of an analgesic before surgery to prevent establishment of central sensitization of pain, is one avenue that has been explored to achieve this. A retrospective observational study was undertaken to examine the effect of pre-emptive paracetamol on intra-operative opioid requirements. The medical and operative data of 156 patients who underwent day-case wide local excision and sentinel lymph node biopsy with and without regional block surgery at our center between October 2019 and May 2022 was carried out. Data were collected on demographics, total intra-operative and immediate post-operative opioid consumption. 57 patients did not receive pre-emptive paracetamol while 90 did. Baseline characteristics were similar. Our results showed a statistically significant reduction in morphine (p <0.029) and remifentanil (p <0.007) consumption in patients who received a regional block and pre-emptive paracetamol. Those who did not receive a regional block and were given pre-emptive paracetamol had a decrease in OxyNorm (p <0.022) requirements. A combination of general anesthesia (GA), regional block and pre-emptive paracetamol reduced intra-operative consumption of Fentanyl, OxyNorm, diclofenac, dexketoprofen, and clonidine (P <0.001) when compared to just GA alone. Use of pre-emptive paracetamol in reduction of intra-operative opioid requirements showed promising results but larger studies may strengthen the evidence for this association. A multimodal analgesic approach that utilizes pre-emptive paracetamol can be a viable method to decrease intra-operative of analgesic requirements.

Association of clinical biomarkers and response to neoadjuvant therapy in breast cancer.

INTRODUCTION: Neoadjuvant therapy is an essential component of multimodality therapy for locally advanced breast adenocarcinoma (BC). Complete pathologic response (pCR) is a useful surrogate for long-term oncologic outcome. AIM: To assess the association between clinicopathologic, molecular and immunological markers and treatment response to neoadjuvant therapy in BC. METHODS: BC patients undergoing neoadjuvant therapy were identified from a prospectively maintained institutional database. Serum haematological/biochemical values, histopathologic, immunohistochemical data and TNM stage were obtained from electronic records. Patients were categorised into complete responders vs non-complete responders and responders vs non-responders. Statistical analysis was performed via SPSS. RESULTS: Overall, 299 BC patients were included. The average age was 49.8 ± 11.5 years. A pCR was evident in 22.6% (n = 69). pCR was associated with early T stage and non-luminal subtypes (HER2 enriched [HER2 +] and triple negative [TNBC]). The neutrophil-lymphocyte ratio (NLR) pre-operatively was lower in patients with a pCR (p = 0.02). The lymphocyte-CRP ratio (LCR) was also slightly reduced in responders (p = 0.049) at diagnosis. A pre-op NLR greater than 2 was not found to be a significant predictive factor (p = 0.071) on multivariable logistic regression analysis. T stage at diagnosis (p = 0.024), N stage (p = 0.001) and breast cancer subtype (p = 0.0001) were also determined to be significant predictive factors of complete response. CONCLUSION: pCR was more likely in patients with less advanced disease in BC. The presence of HER2 + or TNBC in BC also increases the likelihood of pCR. Neoadjuvant therapy stimulates the systemic inflammatory response; however, a reduced baseline NLR may be associated with increased pCR. Confirmation with larger datasets is required.

The prognostic significance of nodal ratio on breast cancer recurrence and its potential for incorporation in a new prognostic index.

Axillary nodal status is an inherent part of prognostic tools such as the Nottingham Prognostic Index (NPI). Literature suggests that nodal ratio is a stronger predictive parameter than the total number of positive nodes sampled. Studies also note improved survival in node-negative patients with a larger proportion of nodes excised. The aim of this study was to assess disease-free survival (DFS) comparing the number of negative and positive nodes excised and nodal ratio as the predictive parameters. Consecutive axillary lymph node dissections (ALND) were analyzed over a 25-year period. Data were analyzed using Cox Regression and Kaplan-Meier survival curves. Eight hundred and forty-nine ALNDs were identified, with 327 positive ALNDs and 268 node negative ALNDs incorporated in the study following exclusions. A prognostic index based on nodal ratio was devised and applied retrospectively to 327 positive ALNDs prior to 2002. This index was then prospectively validated in 116 consecutive positive ALNDs from 2002 to 2005. In node negative ALNDs, no significant difference in DFS was noted in patients having

A pilot study investigating feasibility of mainstreaming germline BRCA1 and BRCA2 testing in high-risk patients with breast and/or ovarian cancer in three tertiary Cancer Centres in Ireland.

In the Republic of Ireland (ROI), BRCA1/BRCA2 genetic testing has been traditionally undertaken in eligible individuals, after pre-test counselling by a Clinical Geneticist/Genetic Counsellor. Clinical Genetics services in ROI are poorly resourced, with routine waiting times for appointments at the time of this pilot often extending beyond a year. The consequent prolonged waiting times are unacceptable where therapeutic decision-making depends on the patient's BRCA status. "Mainstreaming" BRCA1/BRCA2 testing through routine oncology/surgical clinics has been implemented successfully in other centres in the UK and internationally. We aimed to pilot this pathway in three Irish tertiary centres. A service evaluation project was undertaken over a 6-month period between January and July 2017. Eligible patients, fulfilling pathology and age-based inclusion criteria defined by TGL clinical, were identified, and offered constitutional BRCA1/BRCA2 testing after pre-test counselling by treating clinicians. Tests were undertaken by TGL Clinical. Results were returned to clinicians by secure email. Onward referrals of patients with uncertain/pathogenic results, or suspicious family histories, to Clinical Genetics were made by the treating team. Surveys assessing patient and clinician satisfaction were sent to participating clinicians and a sample of participating patients. Data was collected with respect to diagnostic yield, turnaround time, onward referral rates, and patient and clinician feedback. A total of 101  patients underwent diagnostic germline BRCA1/BRCA2 tests through this pathway. Pathogenic variants were identified in 12 patients (12%). All patients in whom variants were identified were appropriately referred to Clinical Genetics. At least 12 additional patients with uninformative BRCA1/BRCA2 tests were also referred for formal assessment by Clinical Geneticist or Genetic Counsellor. Issues were noted in terms of time pressures and communication of results to patients. Results from a representative sample of participants completing the satisfaction survey indicated that the pathway was acceptable to patients and clinicians. Mainstreaming of constitutional BRCA1/BRCA2 testing guided by age- and pathology-based criteria is potentially feasible for patients with breast cancer as well as patients with ovarian cancer in Ireland.

Locoregional recurrence after breast cancer surgery: a systematic review by receptor phenotype.

Molecular subtyping confirms that breast cancer comprises at least four genetically distinct entities based on the expression of specific genes including estrogen receptor (ER), progesterone receptor (PR), and HER2/neu receptor. The quantitative influence of subtype on ipsilateral locoregional recurrence (LRR) is unknown. The aim of this study was to systematically appraise the influence of breast cancer subtype on LRR following breast conserving therapy (BCT) and mastectomy. A comprehensive search for studies examining outcomes after BCT and/or mastectomy according to breast cancer subtype was performed using Medline and cross-referencing available data. Reviews of each study were conducted and data extracted to perform meta-analysis. Primary outcome was LRR related to breast cancer subtype. A total of 12,592 breast cancer patients who underwent either BCT (n = 7,174) or mastectomy (n = 5,418) were identified from 15 studies. Patients with luminal subtype tumors (ER/PR +ve) had a lower risk of LRR than both triple-negative (RR 0.38; 95% CI 0.23-0.61); and HER2/neu-overexpressing (RR 0.34; 95% CI 0.26-0.45) tumors following BCT. Luminal tumors were also less likely to develop LRR than HER2/neu-overexpressing (OR 0.69; 95% CI 0.54-0.89) or triple-negative tumors (OR 0.61; 95% CI 0.46-0.79) after mastectomy. HER2/neu-overexpressing tumors have increased risk of LRR compared to triple-negative tumors (RR 1.44; 95% CI 1.06-1.95) following BCT but there was no difference in LRR between HER2/neu-overexpressing and triple-negative tumors following mastectomy (RR 0.91; 95% CI 0.68-1.22). Luminal tumors exhibit the lowest rates of LRR. Patients with triple-negative and HER2/neu-overexpressing breast tumors are at increased risk of developing LRR following BCT or mastectomy. Breast cancer subtype should be taken into account when considering local control and identifies those at increased risk of LRR, who may benefit from more aggressive local treatment.

A Novel Surrogate Nomogram Capable of Predicting OncotypeDX Recurrence Score©.

Background: OncotypeDX Recurrence Score© (RS) is a commercially available 21-gene expression assay which estimates prognosis and guides chemoendocrine prescription in early-stage estrogen-receptor positive, human epidermal growth factor receptor-2-negative (ER+/HER2−) breast cancer. Limitations of RS testing include the cost and turnaround time of several weeks. Aim: Our aim is to develop a user-friendly surrogate nomogram capable of predicting RS. Methods: Multivariable linear regression analyses were performed to determine predictors of RS and RS > 25. Receiver operating characteristic analysis produced an area under the curve (AUC) for each model, with training and test sets were composed of 70.3% (n = 315) and 29.7% (n = 133). A dynamic, user-friendly nomogram was built to predict RS using R (version 4.0.3). Results: 448 consecutive patients who underwent RS testing were included (median age: 58 years). Using multivariable regression analyses, postmenopausal status (ß-Coefficient: 0.25, 95% confidence intervals (CIs): 0.03−0.48, p = 0.028), grade 3 disease (ß-Coefficient: 0.28, 95% CIs: 0.03−0.52, p = 0.026), and estrogen receptor (ER) score (ß-Coefficient: −0.14, 95% CIs: −0.22−−0.06, p = 0.001) all independently predicted RS, with AUC of 0.719. Using multivariable regression analyses, grade 3 disease (odds ratio (OR): 5.67, 95% CIs: 1.32−40.00, p = 0.037), decreased ER score (OR: 1.33, 95% CIs: 1.02−1.66, p = 0.050) and decreased progesterone receptor score (OR: 1.16, 95% CIs: 1.06−1.25, p = 0.002) all independently predicted RS > 25, with AUC of 0.740 for the static and dynamic online nomogram model. Conclusions: This study designed and validated an online user-friendly nomogram from routinely available clinicopathological parameters capable of predicting outcomes of the 21-gene RS expression assay.

Comparison of the Nottingham Prognostic Index and OncotypeDX© recurrence score in predicting outcome in estrogen receptor positive breast cancer.

INTRODUCTION: Traditionally, Nottingham prognostic index (NPI) informed prognosis in patients with estrogen receptor positive, human epidermal growth factor receptor-2 negative, node negative (ER+/HER2-/LN-) breast cancer. At present, OncotypeDX© Recurrence Score (RS) predicts prognosis and response to adjuvant chemotherapy (AC). AIMS: To compare NPI and RS for estimating prognosis in ER + breast cancer. METHODS: Consecutive patients with ER+/HER2-/LN- disease were included. Disease-free (DFS) and overall survival (OS) were determined using Kaplan-Meier and Cox regression analyses. RESULTS: 1471 patients met inclusion criteria. The mean follow-up was 110.7months. NPI was calculable for 1382 patients: 19.8% had NPI≤2.4 (291/1471), 33.0% had NPI 2.41-3.4 (486/1471), 30.0% had NPI 3.41-4.4 (441/1471), 10.9% had NPI 4.41-5.4 (160/1471), and 0.3% had NPI>5.4 (4/1471). In total, 329 patients underwent RS (mean RS: 18.7) and 82.1% had RS < 25 (270/329) and 17.9% had RS ≥ 25 (59/329). Using multivariable Cox regression analyses (n = 1382), NPI independently predicted DFS (Hazard ratio (HR): 1.357, 95% confidence interval (CI): 1.140-1.616, P < 0.001) and OS (HR: 1.003, 95% CI: 1.001-1.006, P = 0.024). When performing a focused analysis of those who underwent both NPI and RS (n = 329), neither biomarker predicted DFS or OS. Using Kaplan Meier analyses, NPI category predicted DFS (P = 0.008) and (P = 0.026) OS. Conversely, 21-gene RS group failed to predict DFS (P = 0.187) and OS (P = 0.296). CONCLUSION: In our focused analysis, neither NPI nor RS predicted survival outcomes. However, in the entire series, NPI independently predicted both DFS and OS. On the 40th anniversary since its derivation, NPI continues to provide accurate prognostication in breast cancer, outperforming RS in the current study.

Breast cancer recurrence: factors impacting occurrence and survival.

BACKGROUND: Breast cancer mortality has decreased due to improved screening and treatment options. Nevertheless, 25-30% of patients develop disease recurrence and die from the disease dissemination. Patients who develop metastatic disease represent a heterogeneous group and management plans are dependent on molecular subtype, disease burden and metastatic site. AIM: To determine predictive clinicopathological factors of disease recurrence and their impact on survival in the molecular era. METHODS: Consecutive patients who breast cancer developed recurrence at our tertiary referral centre between 2000 and 2015 were included. Clinicopathological and treatment data were assessed using descriptive statistics. Oncological outcome was assessed using Cox regression and Kaplan Meier analyses. RESULTS: Two hundred sixty-five consecutive patients who developed breast cancer recurrence were included; median age at metastasis was 59.3 years (range 27-87 years), and median time to recurrence (TTR) was 47.7 ± 38.5 months (range 3.0-194.3 months). Survival was 24.2% (64/265) 53.2% were luminal A (LABC) (141/265), 18.5% were luminal B (LBBC) (49/265), 18.5% were triple negative (TNBC) (49/265), and 9.8% were human epidermal growth factor receptor-2 overexpressing (HER2 +) (26/265). TTR for patients with LABC was 56.0 ± 41.3 months, LBBC was 48.4 ± 41.1 months, TNBC was 26.9 ± 28.5 months and HER2 + was 34.3 ± 21.8 months. Increased grade (P < 0.001), Nottingham Prognostic Indices (P < 0.001), TNBC (P < 0.001), HER2 + subtype (P < 0.001) and receiving targeted therapy (P = 0.006) predicted shorted TTR. Estrogen receptor positivity (P < 0.001), progesterone receptor positivity (P = 0.010), invasive lobular carcinoma (P = 0.009) and receiving endocrine therapy (P = 0.001) predicted longer TTR. CONCLUSION: Readily available clinicopathological factors predict risk of metastatic dissemination. Developing a tailored program to identify patients at risk of recurrence is crucial in controlling metastatic dissemination of breast cancer.

Bilateral breast cancer: analysis of incidence, outcome, survival and disease characteristics.

There has been conflicting evidence on the impact of bilateral breast cancer (BBC) on the survival and management of patients. The objectives of this study were to address the incidence of BBC and to investigate its characteristics and outcome compared to unilateral cancer. Data were acquired from the prospectively maintained NUIG breast cancer database between 1988 and 2008. BBC were then categorized as synchronous (within 12 months) or metachronous (after 12 months of first tumour). SPSS was used for data analysis. The incidence of BBC in our population was 4.4% (112 of 2,524). Of those 2.1% were synchronous while 2.3% were metachronous. Compared to unilateral cases, bilateral cancer patients were younger (P = 0.021) and had smaller size (P = 0.001) and earlier stage (P < 0.001) tumours at diagnosis. We identified the HER2/neu positivity as a risk factor for developing contralateral breast tumour and ER negativity as a risk factor for developing metachronous tumours. While there was no significant difference in survival for patients with bilateral compared to unilateral tumour (P > 0.05), the synchronous tumour was associated with poorer survival (P = 0.010) in comparison to metachronous tumour. This large single-institutional experience does not support the increasing practice of prophylactic mastectomy but does justify regular follow-up with mammography for early detection of contralateral tumour.

Complementary and alternative medicine use in oncology: a questionnaire survey of patients and health care professionals.

BACKGROUND: We aimed to investigate the prevalence and predictors of Complementary and Alternative Medicine (CAM) use among cancer patients and non-cancer volunteers, and to assess the knowledge of and attitudes toward CAM use in oncology among health care professionals. METHODS: This is a cross-sectional questionnaire survey conducted in a single institution in Ireland. Survey was performed in outpatient and inpatient settings involving cancer patients and non-cancer volunteers. Clinicians and allied health care professionals were asked to complete a different questionnaire. RESULTS: In 676 participants including 219 cancer patients; 301 non-cancer volunteers and 156 health care professionals, the overall prevalence of CAM use was 32.5% (29.1%, 30.9% and 39.7% respectively in the three study cohorts). Female gender (p < 0.001), younger age (p = 0.004), higher educational background (p < 0.001), higher annual household income (p = 0.001), private health insurance (p = 0.001) and non-Christian (p < 0.001) were factors associated with more likely CAM use. Multivariate analysis identified female gender (p < 0.001), non-Christian (p = 0.001) and private health insurance (p = 0.015) as independent predictors of CAM use. Most health care professionals thought they did not have adequate knowledge (58.8%) nor were up to date with the best evidence (79.2%) on CAM use in oncology. Health care professionals who used CAM were more likely to recommend it to patients (p < 0.001). CONCLUSIONS: This study demonstrates a similarly high prevalence of CAM use among oncology health care professionals, cancer and non cancer patients. Patients are more likely to disclose CAM usage if they are specifically asked. Health care professionals are interested to learn more about various CAM therapies and have poor evidence-based knowledge on specific oncology treatments. There is a need for further training to meet to the escalation of CAM use among patients and to raise awareness of potential benefits and risks associated with these therapies.

The effect of breast cancer awareness month on internet search activity--a comparison with awareness campaigns for lung and prostate cancer.

BACKGROUND: This work aimed to assess the effects of the annual breast cancer awareness campaign on internet search activity, and to compare these effects with those of similar campaigns in prostate and lung cancer. We further aimed to assess overall levels of online activity relating to all three neoplasms between 2004 and 2009. METHODS: Google Insights for Search was employed to examine search trends for the term "breast cancer", across all Google domains between January 2004 and December 2009 (6 years). Search trends for both "prostate cancer" and "lung cancer" across all domains were also analysed for the same period, and these trends were compared with those for "breast cancer". Repeated measures ANOVA and Tukey post-hoc analyses were performed to assess for significant differences in activity. RESULTS: Increased levels of online activity relating to breast cancer are consistently generated each October. There is a significantly higher level of background activity in breast cancer compared with that in lung or prostate cancer (p < 0.001), and the October campaign stimulates online activity more effectively than equivalent campaigns for these other malignancies (p < 0.001). CONCLUSIONS: The annual breast cancer awareness campaign is proving effective in stimulating online activity and may hold useful lessons for other cancer awareness initiatives.