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Purpose: To assess the effects of contemporary treatment of ductal carcinoma in situ (DCIS) on the risk of developing an ipsilateral invasive breast cancer (iIBC) in the Dutch female population., Methods: Clinical data was obtained from the Netherlands Cancer Registry (NCR), a nationwide registry of all primary malignancies in the Netherlands integrated with the data from PALGA, the Dutch nationwide network and registry of histo- and cytopathology in the Netherlands, on all women in the Netherlands treated for primary DCIS from 2005 to 2015, resulting in a population-based cohort of 14.419 women. Cumulative iIBC incidence was assessed and associations of DCIS treatment type with subsequent iIBC risk were evaluated by multivariable Cox regression analyses., Results: Ten years after DCIS diagnosis, the cumulative incidence of iIBC was 3.1% (95% CI: 2.6-3.5%) in patients treated by breast conserving surgery (BCS) plus radiotherapy (RT), 7.1% (95% CI: 5.5-9.1) in patients treated by BCS alone, and 1.6% (95% CI: 1.3-2.1) in patients treated by mastectomy. BCS was associated with a significantly higher risk for iIBC compared to BCS + RT during the first 5 years after treatment (HR 2.80, 95% CI: 1.91-4.10%). After 5 years of follow-up, the iIBC risk declined in the BCS alone group but remained higher than the iIBC risk in the BCS + RT group (HR 1.73, 95% CI: 1.15-2.61)., Conclusions: Although absolute risks of iIBC were low in patients treated for DCIS with either BCS or BCS + RT, risks remained higher in the BCS alone group compared to patients treated with BCS + RT for at least 10 years after DCIS diagnosis., (© 2023. The Author(s).)

Purpose: Invasive lobular cancer (ILC) is the second most common histology type of breast cancer followed by invasive ductal carcinoma (IDC). This study aimed to investigate the characteristic, treatment strategies, and clinical outcomes of ILC based on a national population-based cancer registry., Methods: This study recruited 2671 ILC and 52,215 IDC patients diagnosed between 2011 and 2017 using the Taiwan Cancer Registry (TCR). Correlations between ILC and IDC subgroups were assessed using 1:4 propensity score matching and compared using the χ2 test. Disease free survival(DFS) and overall survival(OS) were estimated using the Kaplan-Meier method with the log-rank test. The risk of disease relapse and mortality were assessed using Cox proportional hazards model., Results: ILC patients had larger tumor sizes, more positive axillary lymph node involvement, lower tumor grade, and higher cancer stage than IDC patients. After matching, ILC patients had a significantly higher rate of receiving mastectomy (58.93% and 53.85%) and positive surgical margin regardless of surgery type. ILC exhibited a significantly higher rate of distant metastasis than IDC(3.67% and 2.93%), but no difference in local recurrence rate, DFS or OS between the two groups. Higher cancer stage, higher grade, and mastectomy were risk factors for disease relapse and cancer-specific mortality. The hormone receptor-positive and HER2 over-expression subtypes were found to be associated with a reduced risk of disease relapse, while only PR positivity was associated with a decreased risk of mortality. (all P-values < 0.05)., Conclusion: ILC patients had a higher mastectomy rate, higher surgical margin rate and distant metastasis rate than IDC patients. There is no significant difference in DFS or OS between ILC and IDC patients. Mastectomy was associated with poor outcomes regardless of ILC or IDC., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Neoadjuvant systemic therapy (NAST) can be an effective treatment option for patients with HER2 + or triple negative breast cancer (TNBC). However, its use in geriatric patients is largely understudied. Our aim is to investigate the effect of NAST in both septuagenarians and octogenarians with HER2 + or TNBC to better understand its role in the geriatric patient population., Methods: We utilized the National Cancer Database (NCDB) to analyze female patients with HER2 + or TNBC between 70 and 89 years. We compared the baseline demographic and clinical characteristics of septuagenarians and octogenarians using mixed-effect modeling for continuous variables and conditional logistic regressions for categorical variables. Overall survival (OS) between several subgroups was compared based on a propensity score model. Kaplan-Meier method was used to calculate OS between the subgroups, and log-rank test was used to compare OS results., Results: A total of 16,443 patients met inclusion/exclusion criteria, of which 92.9% had infiltrative ductal carcinoma and 73.5% were TNBC. Most patients received NAST as a first course of therapy (58.8%). Septuagenarians were more likely to receive NAST (65.9%), whereas octogenarians were more likely to receive upfront surgical resection (67.7%). Our analysis demonstrated OS benefit with NAST among patients who received surgical resection. However, in patients who received NAST, decline during therapy was associated with a significantly poorer OS outcomes in general., Conclusion: When combined with surgical resection, NAST is an effective treatment option in both septuagenarians and octogenarians. Nonetheless, careful selection of NAST recipients in this population remains critical to optimize patient outcome., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To determine the biology, recurrence rate, metastatic patterns and survival times in primary triple-negative breast cancer (TNBC) with focus on the comparison between younger and elderly patients., Methods: Patients with primary TNBC stage I-IV diagnosed from 2007 to 2015 were identified and information on tumor biology, stage, treatment, recurrences and death recorded., Results: A total of 524 patients, median age 60 years (range 24-94) with a median follow-up of 55 months (range 0-129) were identified. Stage was similar in younger (< 40 years) (n = 58) and older (> 74 years) (n = 96) patients (p = 0.37). A statistically significant difference was found concerning histopathologic grade (p = 0.006) and Ki67 (median 80% versus 70%; p = 0.002) but not for LVI (p = 0.9) with more aggressive tumors among younger patients. Adjuvant/neoadjuvant chemotherapy was more frequently given to younger compared with older patients (96% versus 12%; p = 0.0005). Only brain (p = 0.016) and liver (p = 0.047) metastases were more often registered among younger patients while other locations were similar. Shorter survival times, recurrence-free survival (RFS), distant disease-free survival (DDFS) and breast cancer-specific survival (BCSS) were found in the older group, although not after adjusting for adjuvant/neoadjuvant chemotherapy. Most deaths (68%) in the older group were caused by TNBC. When comparing patients > 75 years (n = 92) with ≤ 75 years (n = 432), a worse outcome among older was also observed: RFS (p = 0.00012), DDFS (p = 0.00041), BCSS (p < 0.0001) and survival following distant metastasis (p = 0.0064) CONCLUSIONS: Primary TNBC in younger patients is more often of poor differentiation grade and highly proliferative compared with older patients. The majority of older patients still have grade III tumors with a Ki67 > 60% and outcome is poor. Few older patients in our study were treated with chemotherapy both in adjuvant and palliative setting, underlining the need for more prospective trials and treatment options suitable for this patient population.

Purpose: To determine the intermediate-term impact of diagnosis and treatment of ductal carcinoma in situ of the breast (DCIS) on health services utilization, we compared utilization by cases of DCIS to unaffected controls., Methods: We identified a population-based cohort of Ontario females diagnosed with DCIS between 2010 and 2015. We matched 5 controls without any history of cancer to each case, on the date of diagnosis of the case (the index date), by age, annual mammography history, socioeconomic status, and comorbidity. We identified billing claims and hospital records, during the interval 13 to 60 months prior to, and subsequent to the index date, and computed rates per 100 person-years during both intervals, to conduct a difference-in-differences analysis. We used negative binomial regression to test if the change in rates in health services differed between cases and controls., Results: Visits with a breast diagnosis code, and claims for breast surgery and imaging, were significantly increased among cases compared to controls (all p values < 0.0001) after DCIS;however, there was no increase in visits for anxiety or depression (RR 1.13 (95% CI 0.97, 1.32, p = 0.11), visits to psychiatrists (RR 1.07 (95% CI 0.82, 1.40) p = 0.6), or hospital procedures other than breast surgery (RR 1.10 (95% CI 0.88, 1.37) p = 0.4)., Conclusions: DCIS is associated with more visits and procedures related to the breast compared to controls following diagnosis and treatment, but other health services utilization and visits related to anxiety and depression were not increased.

Purpose: Oxidative stress-responsive kinase 1 (OSR1) plays a crucial role in regulating diverse cellular pathophysiologic functions, including ion homeostasis, development, differentiation, angiogenesis, invasive migration, and metastasis. Regardless, the clinical significance of OSR1 in breast cancer is scarce. The current study was conducted to evaluate the effect of OSR1 on the prognosis of patients with breast cancer with a long-term follow-up., Methods: OSR1 expression in formalin-fixed and paraffin-embedded tissue specimens was analyzed. These specimens were collected from 551 evaluable breast cancer cases by immunohistochemistry (IHC). OSR1 expression was dichotomized based on the H-score in IHC. The effects of OSR1 levels on the clinicopathological attributes and survival prediction in patients with breast cancer were explored., Results: Among 551 specimens, 183 (33.2%) exhibited high expression of OSR1 in tumor cells. High OSR1 levels were markedly correlated with histologic grade (P = 0.035), ER (P < 0.001) and PgR (P = 0.043) expression, lymph node involvement (P < 0.001), TNM stage (P < 0.001), and axillary surgery procedures (P = 0.003). Univariate analysis results indicate that patients with high OSR1 expression had significantly poor overall survival (P < 0.001), distant disease-free survival (P < 0.001), and breast cancer-specific survival (P < 0.001). Multivariable Cox regression analyses suggest that OSR1 expression was an independent predictive marker of poor prognosis and lymph node metastasis (HR 3.224, 95% CI 1.182-8.702, P = 0.023) in patients with breast cancer., Conclusions: Our findings indicate that OSR1 is a significantly independent prognosis index for patients with breast cancer with respect to distant disease-free survival, overall survival, and breast cancer-specific survival. High OSR1 expression caused an increase in deaths specifically attributed to breast cancer and was related to increased lymph node metastasis. However, the precise cellular mechanisms for OSR1 in breast cancer require further research.

Purpose: The objective of this study is to analyse the relative survival with breast cancer in women diagnosed after new treatments were generalised and to ascertain the current effect that tumour characteristics such as grade, stage or subtype have on survival as well as the new AJCC-pathological prognostic score., Methods: The breast cancer MCC-Spain follow-up study is a prospective cohort study of 1685 incident breast cancer cases. Women between 20 and 85 years old were recruited between the years 2008 and 2013 in 18 hospitals located in 10 Spanish provinces and they have been followed until 2017/2018. Relative survival was estimated after 3, 5 and 8 years of follow-up using Ederer II method. In addition, Weibull regression adjusted by age, hospital, grade and stage was used to investigate prognosis factors., Results: Among components of TNM staging system, tumour size greater than 50 mm (i.e. T3 or T4) more than doubled the risk of dying, while N3 nodal involvement and presence of metastasis had a huge effect on mortality. The AJCC pathological prognostic score strongly correlated with survival; thus, hazard ratios increased as the score rose, being 2.31, 4.00, 4.94, 7.92, 2.26, 14.9 and 58.9 for scores IB, IIA, IIB, IIIA, IIIB, IIIC and IV, respectively., Conclusion: Both TNM staging and histological/molecular biomarkers are associated with overall survival in Spanish women with breast cancer; when both are combined in the AJCC pathological prognosis score, the prognostic value improved with risk indices that increased rapidly as the pathological prognosis score increased.

Purpose: The aim of this study is to evaluate the prognostic value of the Mitotic Activity Index (MAI) in combination with the human epidermal growth factor receptor (Her2) for distant metastases-free survival (DMFS) and disease-specific survival (DSS) in breast cancer and compare it with the immunohistochemically (IHC) profile types., Methods: Analyses were based on 2.923 breast-conserving breast cancer specimens with known MAI, Her2 status, and hormone receptor status, resulting in 2.678 Her2MAI combinations, MAI ≤ 12/Her2negative, MAI > 12/Her2negative, MAI > 12/Her2positive, and MAI ≤ 12/Her2positive, and 2.560 IHC profile types, luminal A, luminal B, triple negative, and non-luminal Her2positive., Results: For DMFS, the MAI > 12/Her2negative combination showed a significantly worse outcome in multivariate analyses compared to the MAI ≤ 12/Her2negative combination. None of the IHC profile types showed significantly different outcomes for DMFS and DSS as compared to luminal A. We performed a separate analysis on age and lymph node status. The significance of MAI > 12/Her2negative seems to be limited to women ≤ 55 years for both DMFS and DSS. However, with respect to DSS, this seems to be limited to node negative cases. The IHC profile types for DSS, luminal B showed a significantly worse outcome for women > 55 years compared to that for luminal A, although it showed rather wide confidence interval., Conclusion: The MAI > 12/Her2negative combination seems to be a strong prognosticator for DMFS and DSS, particularly for women ≤ 55 years. However, none of the IHC profile types seems to be a prognosticator in breast cancer.

Background: African American women (AAW) die more frequently from estrogen receptor (ER) positive breast cancer than European American women (EAW). We investigated the relationship between race, percent ER staining, treatment, and clinical outcomes., Methods: Percent ER staining (weakly ER+: 1-10%, moderately ER+: 11-50%, strongly ER+: > 50%) was abstracted from pathology reports for 1573 women with ER+/HER2- invasive breast cancer treated at a single cancer center in Detroit, MI from 2010 to 2017. Clinical outcomes and tumor characteristics were obtained from the Metropolitan Detroit Cancer Surveillance System. Associations of ER levels with demographic and clinical characteristics were evaluated using logistic regression. Overall and breast cancer-specific (BCS) survival were evaluated using Cox proportional hazards models., Results: AAW were more likely to have tumors with lower ER staining levels than EAW (weakly ER+: Odds ratio (OR) 2.19, p = 0.019; moderately ER+: OR 2.80, p = 0.005). Women with weakly compared to strongly ER+ tumors were less likely to receive endocrine therapy (ET) regardless of race (OR 0.79, p < 0.001). Mortality was predicted by both AA race (Overall hazard ratio (HR) = 1.72, p < 0.001; BCS HR 1.45, p = 0.08) and low (1-50%) ER (Overall HR 1.57, p = 0.083; BCS HR 2.11, p = 0.017) adjusting for clinic-pathologic characteristics. ET was associated with improved BCS survival in all women (1-50%: HR 0.11, p < 0.001; > 50%: HR 0.24, p < 0.001)., Conclusion: The biology of ER+/HER2- tumors varies by race, although this does not appear to account for racial differences in survival. Although ET substantially reduces mortality among women with weakly ER+ tumors, these women are less likely to be treated with ET and have poorer outcomes.

Purpose: The detection rate of breast ductal carcinoma in situ (DCIS) has increased significantly, raising the concern that DCIS is overdiagnosed and overtreated. Therefore, there is an unmet clinical need to better predict the risk of progression among DCIS patients. Our hypothesis is that by combining molecular signatures with clinicopathologic features, we can elucidate the biology of breast cancer progression, and risk-stratify patients with DCIS., Methods: Targeted exon sequencing with a custom panel of 223 genes/regions was performed for 125 DCIS cases. Among them, 60 were from cases having concurrent or subsequent invasive breast cancer (IBC) (DCIS + IBC group), and 65 from cases with no IBC development over a median follow-up of 13 years (DCIS-only group). Copy number alterations in chromosome 1q32, 8q24, and 11q13 were analyzed using fluorescence in situ hybridization (FISH). Multivariable logistic regression models were fit to the outcome of DCIS progression to IBC as functions of demographic and clinical features., Results: We observed recurrent variants of known IBC-related mutations, and the most commonly mutated genes in DCIS were PIK3CA (34.4%) and TP53 (18.4%). There was an inverse association between PIK3CA kinase domain mutations and progression (Odds Ratio [OR] 10.2, p < 0.05). Copy number variations in 1q32 and 8q24 were associated with progression (OR 9.3 and 46, respectively; both p < 0.05)., Conclusions: PIK3CA kinase domain mutations and the absence of copy number gains in DCIS are protective against progression to IBC. These results may guide efforts to distinguish low-risk from high-risk DCIS.

Purpose: To examine whether pre-diagnosis patient-reported health-related quality of life (HRQOL) and depressive symptoms are associated with local treatment for older women with ductal carcinoma in situ (DCIS) and stage I breast cancer (BC)., Methods: Using the SEER-MHOS dataset, we identified women ≥ 65 years old with DCIS or stage I BC diagnosed 1998-2011 who completed surveys ≤ 24 months before diagnosis. Depressive symptoms were measured by major depressive disorder (MDD) risk and HRQOL was measured by Physical and Mental Component Summary scores (PCS and MCS, respectively) of the SF-36/VR-12. Associations with treatment choice (breast-conserving surgery [BCS] and radiation therapy [RT], BCS alone, mastectomy) were assessed with multivariable multinomial logistic regression, controlling for patient characteristics., Results: We identified 425 women with DCIS and 982 with stage I BC. Overall, 20.4% endorsed depressive symptoms placing them at risk for MDD pre-diagnosis; mean MCS and PCS scores were 52.3 (SD = 10.1) and 40.5 (SD = 11.5), respectively. Among women with DCIS, those at risk for MDD were more likely to receive BCS (adjusted odds ratio [AOR] 2.04, 95% CI 1.04-4.00, p = 0.04) or mastectomy (AOR 1.88, 95% CI 0.91-3.86, p = 0.09) compared to BCS + RT. For DCIS, MCS score was not associated with treatment; higher PCS score was associated with decreased likelihood of receiving mastectomy versus BCS + RT (AOR 0.71 per 10-point increase, 95% CI 0.54-0.95, p = 0.02). For BC, none of the measures were significantly associated with treatment., Conclusion: Older women at risk for MDD before DCIS diagnosis were less likely to receive RT after BCS, compared to BCS alone or mastectomy.

Background: Metaplastic breast cancer (MpBC) is a rare histological subtype of breast cancer recognized as a unique pathologic entity in 2000. However, the pathogenesis, optimal therapy, and prognosis of MpBC and the potential effect of systemic treatments on different subtypes of MpBC are not well defined., Methods: A retrospective population-based study was performed to identify breast cancer patients with MpBC and other triple-negative breast cancers (TNBC) between 2010 and 2014 using the surveillance, Epidemiology, and End Results (SEER) database. Chi-square test was used to analyze characteristics between subgroups. Kaplan-Meier analysis and Multivariate Cox regressions were used to evaluate overall survival (OS) of MpBC, TNBC, and MpBC subgroups. Competing risk analysis and multivariate regression model of competing risk were used to assess breast cancer-specific survival (BCSS) of MpBC and TNBC RESULTS: We identified a study cohort of 22,433 patients (1112 MpBC and 21,321 TNBC). MpBC correlated with older population, larger tumor size and less lymph node involvement, and TNBC phenotype. Patients with MpBC especially with triple-negative subtype (TN-MpBC) had worse survival than the overall TNBC population. However, the prognosis of MpBC without triple-negative subtype (non-TN MpBC) was not different from that of TNBC. In Kaplan-Meier analysis, chemotherapy was not associated with significant difference in OS of TN-MpBC. In non-TN MpBC group, the 3-year OS was 79.8% for patients receiving chemotherapy and 70.5% in patients without chemotherapy, and chemotherapy was associated (P = 0.033) with improved OS. Within the MpBC patients, radiotherapy was significantly (HR 1.544; 95% CI 1.148-2.078; P = 0.004) associated with improved OS and (HR 1.474; 95% CI 1.067-2.040; P = 0.019) BCSS., Conclusions: Patients with TN-MpBC had worse prognosis than TNBC and chemotherapy was not associated with improved survival. In contrast, non-TN MpBC may derive survival benefit from chemotherapy and radiotherapy.

Purpose: The therapeutic effect of systemic treatment for breast cancer (BC) generally depends on its intrinsic subtypes. In addition, tumor infiltrating lymphocytes (TILs) are considered to be an independent factor for tumor shrinkage and disease prognosis. High TILs at baseline or after primary systemic chemotherapy are reported to be associated with better survival in triple-negative or human epithelial growth factor receptor 2 (HER2)-positive BCs. However, the prognostic value of TILs in estrogen receptor (ER)-positive and HER2-negative (ER+/HER2-) BC is still controversial., Methods: We assessed TIL score (low, intermediate, and high) before and after primary systemic chemotherapy in every subtype of BC, and compared the clinical outcomes. Biopsy specimens of 47 triple-negative, 58 HER2+ and 91 ER+/HER2- BCs were used to assess TILs before treatment. To assess TILs after treatment, we examined residual invasive carcinoma in surgically resected samples of 28 triple-negative, 30 HER2+ and 80 ER+/HER2- BCs., Results: A high TIL score in triple-negative BC before treatment resulted in a significantly higher proportion of pathological complete response (pCR). In contrast, ER+/HER2- BC exhibited fewer instances of pCR than other subtypes. Although not statistically significant, ER+/HER2- cases with a high TIL score also tended to achieve pCR (p = 0.088). Moreover, we revealed that low TIL BCs after chemotherapy, but not at baseline, had significantly better relapse-free survival in ER+/HER2- BC (p = 0.034)., Conclusion: Pathological examination of TILs after treatment may be a surrogate marker for prognosis in ER+/HER2- BC.

Objectives: To validate the newly proposed American Joint Committee on Cancer (AJCC) prognostic staging system for breast cancer., Methods: Surveillance, epidemiology, and end results (SEER) database (2010-2014) was accessed. Cumulative incidence function was conducted (through assessment of sub-distribution hazard) according to both anatomical and prognostic stages. Likewise, Cox cause-specific hazard ratio with pairwise hazard ratio comparisons were also assessed for both anatomical and prognostic stages. Survival analyses according to both anatomical and prognostic staging systems were conducted through Kaplan-Meier analysis/log-rank testing., Results: A total of 209,304 patients with non-metastatic breast cancer and upfront surgical treatment were included. According to anatomical stages, pairwise Cox hazard ratio comparisons between different stages were significant (P < 0.0001) except between stage IIIB and stage IIIC, while according to prognostic stages, all pairwise hazard ratio comparisons between different stages were significant (P < 0.05). Sub-distribution hazard ratio (using breast cancer death as the primary failure endpoint and using other causes of death as competing causes of death) adjusted for age, race, and surgery was as follows: for the anatomical groups, it was 1.671 (95% CI 1.627-1.716; P < 0.0001) indicating increasing risk of death from breast cancer with increasing stage; however, for the prognostic groups it was 1.790 (95% CI 1.744-1.838; P < 0.0001) indicating increasing risk of death from breast cancer with increasing stage. C-statistic was assessed using breast cancer death as the dependent variable; and the findings for the two staging systems were as follows: anatomical staging: 0.767 (SE 0.004; 95% CI 0.759-0.776); prognostic staging: 0.814 (SE 0.004; 95% CI 0.807-0.822)., Conclusions: The current analysis showed an improvement in the discriminatory value for the prognostic staging system compared to the anatomical staging system and endorsed its routine use in clinical practice.

Purpose: To investigate whether treatment (surgery, radiation therapy, and endocrine therapy) contributes to racial disparities in outcomes of ductal carcinoma in situ (DCIS)., Patients and Methods: The analysis included 8184 non-Hispanic White and 954 non-Hispanic Black women diagnosed with DCIS between 1996 and 2011 and identified in the Missouri Cancer Registry. Logistic regression models were used to estimate odds ratios (ORs) of treatment for race. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) of ipsilateral breast tumor (IBT) and contralateral breast tumor (CBT) for race., Results: There was no significant difference between Black and White women in utilization of mastectomy (OR 1.16; 95 % CI 0.99-1.35) or endocrine therapy (OR 1.19; 95 % CI 0.94-1.51). Despite no significant difference in underutilization of radiation therapy (OR 1.14; 95 % CI 0.92-1.42), Black women had higher odds of radiation delay, defined as at least 8 weeks between surgery and radiation (OR 1.92; 95 % CI 1.55-2.37). Among 9138 patients, 184 had IBTs and 326 had CBTs. Black women had a higher risk of IBTs (HR 1.69; 95 % CI 1.15-2.50) and a comparable risk of CBTs (HR 1.19; 95 % CI 0.84-1.68), which were independent of pathological features and treatment., Conclusion: Racial differences in DCIS treatment and outcomes exist in Missouri. This study could not completely explain the higher risk of IBTs in Black women. Future studies should identify differences in timely initiation and completion of treatment, which may contribute to the racial difference in IBTs after DCIS.

This single-center prospective study aims to assess the outcomes and the toxicities related to the concurrent administration of trastuzumab (T) with adjuvant locoregional radiotherapy (RT) in localized breast cancer. Data of 308 patients were analyzed. T was delivered every 3 weeks (loading dose of 8 mg/kg, then 6 mg/kg) for 1 year. Left ventricular ejection fraction (LVEF), measured by echocardiography or myocardial scintigraphy, was considered as impaired when below 55%. Toxicities were assessed according to the Common Terminology Criteria for Adverse Events version 3.0. Univariate and multivariate analyses were carried out using the Cox model. Median follow-up was 50.2 months (13.0-126.0). Median age at diagnosis was 52 years (25-83). Internal mammary node (IMN) RT was performed in 227 patients (73.7%). After completion of RT, 26 patients (8.4%) presented an impaired LVEF: 17 (5.5%) of grade 1, 7 (2.3%) of grade 2, and 2 (0.6%) of grade 3. At 48 months, locoregional control rate was 95% [95% CI 92; 98], and overall survival rate was 98% [95% CI 96; 100]. In univariate analysis, neither the treated breast side (p = 0.655) nor IMN RT (p = 0.213) exposed patients to LVEF alteration. In multivariate analysis, clinical lymph node involvement was associated with an increased risk of locoregional and distant recurrence (p = 0.016 and p = 0.007, respectively). In this prospective study, the toxicities of concurrent T with locoregional breast RT were acceptable and the outcomes favorable. Longer follow-up is warranted to confirm these results.

For low-volume tumours, high surgical hospital volume is associated with better survival. For high-volume tumours like breast cancer, this association is unclear. The aim of this study is to determine to what extent the yearly surgical hospital breast cancer volume is associated with overall survival. All patients, diagnosed with primary invasive non-metastatic breast cancer in the period 2001-2005, were selected from the Netherlands Cancer Registry. Hospitals were grouped by their annual volume of surgery for invasive breast cancer. Cox proportional hazard models were used including patient and tumour characteristics as covariates. Follow-up was completed until the 1st of February 2013. Primary endpoint was 10-year overall survival rate. In total, 58,982 patients with invasive non-metastatic breast cancer were diagnosed during the period 2001-2005. Hospitals were grouped by their (mean) annual surgical volume: <75 (n = 19), 75-99 (n = 30), 100-149 (n = 29), 150-199 (n = 9) and ≥200 (n = 14). The 10-year observed survival rates were 77, 81, 80, 82 and 82 %, respectively. After case-mix adjustment, patients in low-volume hospitals had a HR of 1.09 (<75 vs. ≥200; 95 % CI 1.03-1.15). Survival was significantly higher for lobular carcinoma and for diagnosis in the most recent year (2005). Being a male, having a higher age at diagnosis, a higher tumour grade, a larger tumour size, a higher number of positive lymph nodes, an earlier year of diagnosis and a lower SES resulted in a reduced survival and influenced death, all to a larger extent than surgical volume did. In the Netherlands, surgical hospital volume influences 10-year overall survival only marginally and far less than patient and tumour characteristics. No difference in survival was revealed for invasive non-metastatic breast cancer patients in hospitals with 75-99 operations per year compared with hospitals with over 200 operations per year.

Detection of disseminated tumour cells (DTCs) in bone marrow by immunocytochemistry (ICC) includes morphological evaluation of cytokeratin immunopositive cells. The aim of this study was to disclose the prognostic significance of different morphological categories of ICC-positive cells according to treatment status and tumour subtype. Bone marrow samples (at surgery) were analysed for the presence of cytokeratin-positive DTCs by a standard immunocytochemical method. The immunopositive cells were classified into the following categories, prior to any analysis of the association between DTCs and clinical outcome: tumour cells (TC), uninterpretable cells (UIC), hematopoietic cells (HC), and questionable HC (QHC). The analysis included 747 early breast cancer patients. Median follow-up was 84 months for relapse, and 99 months for death. The categorisation of the ICC positive cells revealed TC in 13.3 % of the patients, whereas 13.1, 17.8, and 21.4 % of the cases were positive for UIC, QHC, and HC, respectively. Analysing all patients, only TC and UIC predicted systemic relapse. Separate analysis of all patients not receiving adjuvant systemic treatment (No-Adj; n = 389) showed that only QHC were associated with reduced survival (DDFS: p = 0.008; BCSS: p = 0.004, log rank) and the presence of QHC also remained significant in multivariate analysis. Primary tumour subgroup analysis (of all patients) by hormone receptors (HR) and HER2, demonstrated that only TC/UIC had prognostic impact in the HR+/HER2- patients, whereas presence of QHC was associated with unfavourable outcome only in triple negative patients (DDFS: p = 0.004; BCSS: p = 0.024). Patients with ≥3HC had improved outcome compared to those with fewer/no HC (DDFS: p = 0.005; BCSS: p = 0.009). Hence, morphological DTC subgroups may differ in clinical significance according to primary tumour subtype and treatment status. This emphasises the importance of DTC characterisation, and separate analyses of DTC categories according to tumour subtype. Hematopoietic ("false positive") cells might predict an immune-related favorable clinical outcome.

Invasive ductal carcinoma with lobular features (IDC-L) is not recognized as a distinct subtype of breast cancer, and its clinicopathologic features and outcomes are unknown. In this retrospective study, we focused on characterization of clinicopathologic features and outcomes of IDC-L and compared them to invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). 183 cases of IDC-L from 1996 to 2011 were compared with 1,499 cases of IDC and 375 cases of ILC. Available slides of IDC-L (n = 150) were reviewed to quantify the lobular component (≤ 20, 21-50, 51-80, >80 %), defined as small cells individually dispersed, arranged in linear cords, or in loose aggregates without the formation of tubules or cohesive nests. E-cadherin immunostain was performed to confirm ductal origin. Compared to IDC, IDC-L was more likely to have lower histologic grade (p < 0.001), be positive for estrogen receptor (96 vs. 70 %; p < 0.0001) and progesterone receptor (84 vs. 57 %; p < 0.0001), and less likely to overexpress HER-2/neu (12 vs. 23 %; p = 0.001). Despite these favorable prognostic features, IDC-L had a higher frequency of nodal metastases (51 vs. 34 %; p < 0.0001) and a worse 5-year disease-free survival than IDC (hazard ratio = 0.454; p = 0.0004). ILC and IDC-L had similar clinicopathologic features and outcomes. The proportion of the lobular component in IDC-L had no impact on the size, nodal status, stage, or outcome. Our data suggest that although IDC-L may be a variant of IDC, with >90 % of cases being E-cadherin positive, the clinical and biological characteristics are more similar to that of ILC.

High proliferation rates are characteristic of cancer, and proliferation markers make up the majority of genes included in RNA-based prognostic gene signatures applied for breast cancer patients. Based on prior data on differences in molecular subgroups of breast cancer, we hypothesized that the significance of single proliferation markers might differ in luminal, Her2-positive and triple-negative subtypes. Therefore, we compared mRNA expression data of Ki67, TOP2A, and RacGAP1 using a pool of 562 Affymetrix U133A microarrays from breast cancer samples. "Luminal," "triple-negative," and "Her2-positive" subcohorts were defined by ESR1 and ERBB2 mRNA expression using pre-defined cut-offs. The analysis of the three potential proliferation markers revealed subtype-specific differences: in luminal carcinomas, expression of all three markers was a significant indictor of early recurrence in univariate and multivariate analysis, but RacGAP1 was superior to Ki67 and TOP2A in significance. In triple-negative tumors, only Ki67 was a significant and independent marker, whereas none of the markers showed a significant prognostic impact in Her2-positive cases. Within the group of luminal carcinomas, the proliferation markers had different impact depending on the treatment of patients: in untreated patients, Ki67, TOP2A, and RacGAP1 were significant and independent prognostic markers. In chemotherapy-treated patients, overexpression of all three markers was predictive for early recurrence, but only RacGAP1 retained significance in multivariate analysis. In contrast, RacGAP1 was the only predictive proliferation marker in the endocrine treatment group. These data point to subtype-specific differences in the relevance of proliferation-associated genes, and RacGAP1 might be a strong prognostic and predictive marker in the luminal subgroup.

Adjuvant chemotherapy significantly decreases recurrences and improves survival in women with early breast cancer (BC). However, the side effects of chemotherapy include weight gain, which is associated with poorer prognosis. We have previously demonstrated that by means of a comprehensive dietary modification which aims at lowering insulin levels it is possible to reduce body weight and decrease the bioavailability of insulin, sex hormones and the growth factors linked to BC risk and prognosis. We are now going to present a randomized controlled study of adjuvant diet in BC patients undergoing chemotherapy. The diet was designed to prevent weight gain during chemotherapy treatment. Women of any age, operated for invasive BC, scheduled for adjuvant chemotherapy and without evidence of distant metastases, were randomized into a dietary intervention group and a control group. The intervention implied changing their usual diet for the whole duration of chemotherapy, following cooking classes and having lunch or dinner at the study centre at least twice per week. 96 BC patients were included in the study. The women in the intervention group showed a significant reduction in their body weight (2.9 kg on average), compared with the controls. They also significantly reduced body fat mass, waist and hip circumferences, biceps, underscapular and suprailiac skinfolds, compared with the women in the control group. Our results support the hypothesis that dietary intervention during adjuvant chemotherapy for BC is feasible and may prevent weight gain.

It has been reported that the prognostic significances of tumor-infiltrating FOXP3(+) regulatory T cells (Tregs) in breast carcinoma depend on their relative density and tissue locations. We here assessed the changes of Tregs before and after neoadjuvant chemotherapy (NC) and their relationships with tumor response and patient survival. Intratumoral and peritumoral infiltration of FOXP3(+) Tregs were evaluated by immunohistochemistry in 132 cases of invasive breast carcinomas before and after NC. After NC, the density of infiltrated Tregs within tumor bed remained stable, whereas it decreased significantly (P = 0.015) in the tissue surrounding tumor. The changes were significant in those tumors that usually response to NC, including the HER2-enriched and basal-like subtypes (P = 0.035; P = 0.004). Univariate and multivariate analyses identified the decreased peritumoral Tregs were an independent predictor for pathologic complete response (pCR), while the intratumoral Tregs after chemotherapy was proved to be associated with overall survival and progression-free survival of the patients. The findings of the study indicated that peritumoral Treg was sensitive to chemotherapy and associated with pCR, while intratumoral Treg was an independent prognostic predictor of breast cancer patients.

Routine removal of the internal mammary chain (IMC) sentinel node in breast cancer patients remains a subject of discussion. The aim of this study was to determine the impact of routinely performed IMC sentinel node biopsy on the systemic and locoregional treatments plan. All patients with biopsy proven breast cancer who underwent a sentinel node procedure between 2002 and 2011 were included in a prospective database. In cases of IMC drainage, successful exploration of the IMC (i.e., sentinel node removed) and surgical complications were registered. If the removed sentinel node contained malignant cells we determined if this altered the treatment plan when practising the current guidelines. In total, 119 of the 493 included patients showed IMC drainage on lymphoscintigraphy. Exploration of the IMC was performed in 107 (89 %) patients; in 86/107 (80 %) exploration was successful. In 14/107 patients (13 %) the IMC sentinel node was tumor positive. Macro and micro metastases were found in eight and six patients, respectively. In the group of patients who underwent surgical exploration of the IMC, systemic treatment was changed in none, radiotherapy treatment in 13/107 patients (11 %). Routine sentinel node biopsy of the IMC does not alter the systemic treatment. Radiotherapy treatment is altered in a small proportion of the patients; however, solid scientific evidence for this adjustment is lacking.

The aim of this analysis was to investigate the usefulness of Ki-67 labeling index (LI) for the identification of different prognostic subgroups in primary node-negative, triple negative breast cancer (TNBC) patients. From January 1997 to December 2005, 1,053 patients operated for TNBC were identified through the institutional clinical database. The study was performed in accordance with REMARK criteria. The relationship between Ki-67LI and the risk of breast-related deaths was evaluated with a multivariable Cox regression model. Cubic splines were used to model Ki-67LI as a continuous variable. We selected 496 consecutive patients with node-negative TNBC. Median age was 52 years, median Ki-67LI 48% (range 4-95), and median follow up 6 years (range 0.5-13). Total deaths and deaths from BC were 52 (10.5%) and 38 (7.7%), respectively. Ki-67LI increased with decreasing age (P<0.01), increasing tumor size (P<0.01), and grade (P<0.01). When analyzing Ki-67LI as a continuous variable, the risk of death from BC increased steeply with increasing Ki-67LI up to about 35% and remained flat for higher values (adjusted effect of Ki-67 P=0.049; adjusted nonlinear effect P=0.021). Accordingly, when dividing patients into lower (≤35%) and higher (>35%) Ki-67LI subgroups, the 5-year cumulative incidence of breast-related deaths were 2.3 and 9.0%, respectively, with an adjusted HR(>35 vs ≤35) of 2.3 (95% CI 1.0-5.8, P=0.046). Within the group of patients with node-negative TNBC, Ki-67LI was associated with different prognoses subgroups. Ki-67LI might be useful in the design of trials of risk-adapted adjuvant therapies.

The goal of the present study was to evaluate the role of the tyrosine kinase receptor fibroblast growth factor-1 (FGFR1) and its ligand, the fibroblast growth factor 2 (FGF2) in determining the response to chemoradiotherapy of breast cancers. S14 was a phase II neoadjuvant study carried out at the Institut Curie that recruited 59 patients between November 2001 and September 2003. This prospective study aimed to assess the pathological response after preoperative radiochemotherapy (5FU-Navelbine-radiotherapy) for large breast cancers. The expression of FGFR1 and FGF2 in tumor cells were assessed by immunohistochemistry. Tumors in which no staining was seen, were considered as negative for that protein. We used the Khi-2 test or the Fisher test to compare the qualitative variables and the Student t test or the non-parametric Wilcoxon test for the quantitative variables. We included in the present study all the 32 patients from the S14 cohort for whom the tissue blocks from the biopsy specimens were available with sufficient tumoral tissue. FGFR1 and FGF2 staining were observed respectively in 17 (56%) and 22 (68%) of the 32 tumoral biopsies. The expression of FGFR1 was associated with the hormone receptor positive status (p=0.0191). Only 11% (1/9) of the high grade tumors failed to respond to chemoradiotherapy compared to 68 % resistant tumors (15/22) among the low/intermediate grade tumors (p=0.0199). Among the low/intermediate grade tumors, FGFR1 negative tumors did not respond to chemoradiotherapy (0/9), compared with tumors expressing FGFR1 among which, almost one half had a good response (6/13) (p=0.0167). Among the low and intermediate grade breast cancers, the FGFR1 negative tumors were resistant to chemoradiotherapy. The expression of FGFR1 in patients' biopsies may serve as a marker of response to chemoradiotherapy.

To evaluate if biologically effective dose (BED), and in particular the duration of radiation treatment, has an effect on local relapse risk. Between January 2000 and December 2008 a total of 762 patients with T1-2 N0/+ breast cancer was treated with breast-conserving surgery and radiotherapy, with and without hormone therapy and chemotherapy. Adjuvant radiation therapy was administered to a total dose of 60-66 Gy in 30-33 fractions. The computed BEDs were divided in four groups: <43.1, 43.1-44.9, 45.0-46.1, and >46.1 Gy (A-D, respectively). Kaplan-Meier method was used to calculate local relapse rates. Cox regression method was used to identify prognostic factors of local relapse. Evaluated variables were age, tumor histology, tumor size, surgical margin status, axillary nodal status, tumor grading, adjuvant therapies, adjuvant chemotherapy alone, adjuvant hormone therapy alone, adjuvant anthracyclines, and BEDs values. 8-year local relapse rates were 18.0% for group A, 8.5% for group B, 4.6% for group C, and 2.7% for group D (P=0.008). Multivariate Cox regression analysis showed that BEDs values were associated with higher local relapse risk (P=0.001). In our study, a prolongation of radiotherapy treatment, intended as a lower BED value, after breast-conserving surgery is associated with an increased risk of local relapse. Considering the wide range of results published in other studies, hypofractionation for breast cancer should be considered, at the moment, feasible in selected patients.

Triple-negative breast cancer (TNBC) (ER-/PGR-/erb-2-) constitutes an aggressive subtype in breast cancer because it is accompanied by a significant decrease in overall survival (OAS) and recurrence-free survival (RFS) compared with hormone receptor positive breast cancers. This retrospective cohort study investigates the following issues: (1) Is there an impact of guideline-adherent treatment on RFS and OAS in TNBC? (2) Which adjuvant treatment has the most important impact on RFS and OAS in TNBC? This German retrospective multi-centre cohort study included 3,658 patients with primary breast cancer recruited from 2000 to 2005. The definition of guideline adherence was based on the German national S3 guideline for diagnosis and treatment of breast cancer (2004). A total of 371 patients (10.1%) had TNBC. Compared with HR+/erb-2- breast cancer (P = 0.001; HR = 1.75; 95% CI: 1.27-2.40), the recurrence rate of TNBC was significantly higher (P < 0.001; HR = 2.86; 95% CI: 2.17-3.76). Furthermore, the 5-year RFS and OAS was significantly lower in TNBC (RFS: 74.8% [95% CI: 68.8-80.8%] vs. 86.5% [95% CI: 84.6-88.4%] [log-rank P = 0.0001]) (OAS: 75.8% [95% CI: 69.9-81.8%] vs. 86.0% [95% CI: 84.1-87.9%] [log-rank P = 0.0001]). The most important parameters predicting RFS and OAS in TNBC after receiving guideline-conform chemotherapy are guideline-adherent surgery, radiotherapy, nodal status and grading. Overall, 66.8% TNBC were found with one or more (18%) guideline violations, which subsequently impaired OAS and RFS. The most important impact on OAS and RFS in TNBC patients was because of guideline violations (GV) concerning adjuvant radiotherapy and GV concerning adjuvant chemotherapy. Patients with TNBC primarily have a worse prognosis in terms of RFS and OAS than patients of a primarily non-TNBC phenotype. There is a strong association between guideline-adherent adjuvant treatment and improved survival outcome in TNBC. The outcome significantly decreases with the number of guideline violations.

Young breast cancer patients are more likely than old patients to experience ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS). However, the pathological processes underlying this relationship have not been elucidated. We investigated the effect of young age on IBTR in a Korean cohort of women with different molecular subtypes of breast cancer. We analyzed data of 2,102 consecutive breast cancer patients who underwent BCS and post-surgical radiation therapy (RT) at two Korean institutions between 2000 and 2005. Patients were classified as young (≤ 40 years; N = 513) or old (> 40 years; N = 1,589). Breast cancer subtype was determined by estrogen receptor (ER), progesterone receptor (PR), and HER2. Median follow-up duration was 61 months. The 5-year IBTR rate was 3.4% in young patients and 1.1% in old patients (P < 0.001). Univariate analysis indicated that IBTR rate in young patients with luminal A and HER2 subtypes was significantly greater than in old patients with these subtypes (P = 0.015 and P < 0.001, respectively). Multivariate analysis, which used luminal A subtype in old patients as reference, indicated that HER2 subtype in young patients was associated with increased risk of IBTR (hazard ratio, HR = 12.24; 95% CI: 2.54-57.96). Among old patients, HER2 subtype was not associated with increased IBTR. In conclusion, young women had a higher rate of IBTR after BCS and RT than old women. This difference is mainly among women with HER2 subtype. Aggressive local control and adjuvant therapy should be considered for young women with HER2 subtype breast cancer.

Immunohistochemical markers are often used to classify breast cancer into subtypes that are biologically distinct and behave differently. The aim of this study was to estimate relapse for patients with the major subtypes of breast cancer as classified using immunohistochemical assay and to investigate the patterns of benefit from the therapies over the past years. The study population included primary, operable 2,118 breast cancer patients, all non-specific infiltrative ductal carcinoma, with the median age of 53.2 years. All patients underwent local and/or systemic treatments. The clinicopathological characteristics and clinical outcomes were retrospectively reviewed. The expression of estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and cytokeratin 5/6 were analyzed by immunohistochemistry. All patients were classified into the following categories: luminal A, luminal B, HER2 overexpressing, basal-like, and unclassified subtypes. Ki-67 was detected in luminal A subtype. The median follow-up time was 67.9 months. Luminal A tumors had the lowest rate of relapse (12.7%, P < 0.001), while luminal B, HER2 overexpression, and basal-like subtypes were associated with an increased risk of relapse (15.7, 19.1, 20.9%). Molecular subtypes retained independent prognostic significance (P < 0.001). In luminal A subtype, adjunctive radiotherapy could decrease the risk of relapse (P = 0.005), Ki67 positive was a high-risk factor for relapse (P < 0.001), and adjuvant chemotherapies could reduce the relapse for the patients with risk factors (P < 0.001). Adjuvant hormone therapy was an effective treatment for ER-positive tumors (P < 0.001). Molecular subtypes of breast cancer could robustly identify the risk of recurrence and were significant in therapeutic decision making. The model combined subtype and clinical pathology was a significant improvement. Luminal A tumors might represent two distinct subsets which demonstrated distinct prognosis and therapy response.

The insulin-like growth factor type 1 receptor (IGF1R) is involved in progression of breast cancer and resistance to systemic treatment. Targeting IGF1R signaling may, therefore, be beneficial in systemic treatment. We report the effect of IGF1R expression on prognosis in invasive ductal breast carcinoma (IDC), the most common type of breast cancer. Immunohistochemistry was performed on tumor tissue of a consecutive cohort of 429 female patients treated for operable primary IDC. Associations between IGF1R expression with clinicopathological parameters, disease free survival (DFS) and breast cancer specific survival (BCSS) were evaluated by multivariate analyses focusing on ER-positive and triple negative IDC (TN-IDC). To enlarge the TN-IDCs cohort, we analyzed a combined dataset of 51 TN-IDC tumors from our series with 64 TN-IDCs with similar clinicopathological parameters. Patients with tumors expressing cytoplasmic IGF1R have a longer DFS and BCSS (DFS: HR 0.46, 95% CI 0.27-0.49, P = 0.005, BCSS: HR 0.38, 95% CI 0.19-0.74, P = 0.005). This effect was most prominent in ER-positive tumors. However, in a combined series of 105 TN-IDCs cytoplasmic IGF1R expression was associated with a shorter DFS (HR = 2.29, 95% CI 1.08-4.84, P = 0.03), also when combined in a multivariate model, including well-known prognostic factors (HR 2.06; 95% CI 0.95-4.47; P = 0.07). IGF1R expression in ER-positive IDC is strongly related to a favorable DFS and BCSS, but to a shorter DFS in TN-IDC tumors. This divergent effect of IGF1R expression in subgroups of IDC may affect selection of patients for IGF1R targeted therapy.

To report an unanticipated pregnancy during ovarian ablation treatment with goserelin (10.8 mg SC every 12 weeks) in a 26-year old female with breast cancer. Review of the current literature and reports in MEDLINE, PubMED, and EMBASE using searches with keywords "goserelin, pregnancy, breast cancer, breast neoplasms, fertility, ovarian ablation, gonadotropin releasing hormone agonists/analogs, leuprolide, pregnancy complications, teratogens" (July-September 2010). Only 3 other reports of failures with goserelin administration at ablative doses in breast cancer patients were discovered. For physicians and breast cancer patients using a GnRH analog, it is important to be aware of the possibility of inadequate ovarian function suppression and the potential for pregnancy.

The management of ductal intraepithelial neoplasia (DIN) has substantially changed over the past 30 years, as its incidence has increased (from 2-3% to more than 20%), mainly due to the widespread use of mammography screening. This article describes not only the more widespread theoretical concepts on DIN but also the differences in the practical applications of the theory between different countries, different oncology specialists, and different cancer centers. Papers related to the international multicentre-randomized trials and retrospective studies were analyzed. We include articles and papers published between 1993 and 2010 related to patients with DIN, and abstracts and reports from MEDLINE and other sources were indentified. The standard of care for DIN consists of (a) breast conservative surgery (mastectomy is still indicated in large lesions--masses or microcalcifications--in about 30% of cases); (b) radiotherapy (RT) after conservative surgery, and (c) medical treatment in estrogen receptors-positive patients. However, most studies have shown significant differences between theory and practical application. Moreover, there are differences regarding (a) the indications of sentinel lymph node biopsy, (b) the definition and identification of low-risk DIN subgroups that can avoid RT and tamoxifen, and (c) the research into new alternative drugs in adjuvant medical therapy. A general agreement on the best management of DIN does not exist as yet. New large trials are needed in order to define the best management of DIN patients which is (in most respects) still complex and controversial.

While ductal carcinoma in situ (DCIS) is seldom life threatening, the management of DCIS remains a dilemma for patients and their physicians. Aggressive treatment reduces the risk of ipsilateral breast tumor recurrence (IBTR), but has never been proven to improve survival. There is interest in identifying the prognostic factors for determining low-risk DCIS patients, but a comprehensive review of high-quality evidence on tumor characteristics in predicting local recurrence has never been carried out. We examined the following tumor characteristics: biomarkers, comedonecrosis, focality, surgical margin, method of detection, tumor grade, and tumor size. For this systematic review we restricted the analyses to the results of subgroup analyses from randomized controlled trials (RCTs) and multivariate analyses from RCTs and observational studies. We identified 44 eligible articles. The pooled random-effects risk estimates for IBTR are comedonecrosis 1.71(95% CI, 1.36-2.16), focality 1.95(95% CI, 1.59-2.40), margin 2.25(95% CI, 1.77-2.86), method of detection 1.35(95% CI, 1.12-1.62), tumor grade 1.81(95% CI, 1.53-2.13), and tumor size 1.63(95% CI, 1.30-2.06). Limited evidence indicated that women whose DCIS is ER-negative, PR-negative, or HER2/neu receptor positive have an IBTR higher than those whose DCIS is ER-positive, PR-positive, and HER2/neu receptor negative. A variety of tumor characteristics are significant predictors for IBTR. These results are important for both clinicians and patients to interpret the risk of local recurrence and to decide on a course of treatment.

Patients with large ER positive tumors candidate to preoperative chemotherapy may also benefit from a concurrent endocrine intervention, but this issue has been scarcely investigated due to concerns arising from unfavorable results emerged from an adjuvant trial of concurrent tamoxifen and chemotherapy. We retrospectively investigated the activity of letrozole plus GnRH analogue (GnRH-a) administered concurrently with preoperative chemotherapy and as adjuvant treatment in premenopausal women with locally advanced ER positive breast cancer consecutively admitted at the European Institute of Oncology. Results were compared with those of a non-randomized unmatched control group of premenopausal women with locally advanced ER positive breast cancer receiving preoperative chemotherapy, followed by tamoxifen and GnRH-a after surgery. Primary endpoints were pathological complete response (pCR) rate, decrease of Ki67 and disease free survival (DFS). One-hundred and nineteen women constituted the study group, while 95 patients served as controls. The pCR rate was 5.0 vs 1.1% in the study and control group, respectively. A statistically significant greater suppression of Ki67 was observed in patients receiving chemoendocrine therapy as compared with controls (P = 0.003). At a median follow up of 59 months, 26 events occurred in the chemoendocrine group and 48 in the control group. Five-year DFS was 78 vs 41% in the study and in the control group, respectively [adjusted HR 0.46, 95% CI 0.27-0.79, P = 0.0047]. The concurrent administration of letrozole and GnRH-a with preoperative chemotherapy was highly effective in premenopausal women with large ER positive breast cancer in terms of decreased proliferation and of improved DFS. Randomized studies are warranted to establish the role of the addition of endocrine therapy to chemotherapy as standard preoperative approach for ER positive locally advanced breast cancer as well as of letrozole in combination with GnRH-a for the treatment of premenopauasal women with early breast cancer.

Metaplastic breast carcinoma (MBC) is a rare, heterogeneous breast cancer characterized by admixture of adenocarcinoma with metaplastic elements, low hormone receptor expression, and poor outcomes. The authors retrospectively reviewed the medical records of 47 MBC patients and 1,346 invasive ductal carcinoma (IDC) patients. Two hundred eighteen of the IDC patients were triple-negative (TN-IDC) for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 (ER-/PR-/HER2-). Patients were surgically treated at the Samsung Medical Center between 2005 and 2009. The MBC patients presented with a larger tumor size, lower lymph node involvement, higher histological and nuclear grades, higher triple negativity (ER-/PR-/HER2-) and higher p53, CK5/6, and EGFR expressions compared with those of the IDC group. However, there were no significant differences in clinicopathological characteristics between MBC and TN-IDC. During the follow-up period (median duration of 30.3 months, range 2.6-56.3 months), seven (14.9%) MBC patients, and 98 (7.1%) IDC patients had disease recurrence. The three-year disease-free survival (DFS) rate was 78.1% in the MBC group and 91.1% in IDC group (P < 0.001). The three-year DFS rate was not significantly different between the MBC and TN-IDC groups (78.1 vs. 84.9%, P = 0.114). However, in patients with lymph node metastasis who underwent adjuvant chemotherapy, the three-year DFS rate was 44.4% in the MBC group and 72.5% in the TN-IDC group (P = 0.025). The authors found that MBC had a poorer clinical outcome than did IDC. In breast cancer patients with nodal metastasis, MBC had a poorer prognosis than did TN-IDC, despite adjuvant chemotherapy.

For classification of breast cancer (BC), tumor-node-metastasis (TNM) staging has been considered state of the art for more than 50 years. The T category is well defined, and in multicentric and multifocal tumors, tumor size is assessed by the largest tumor focus. The aim of this study was to compare multicentric/multifocal tumor spread in breast cancer with unifocal disease and to evaluate the diagnostic relevance of multifocality. A retrospective analysis was performed on survival related events in a series of 5,691 breast cancer patients between 1963 and 2007. By matched-pair analysis, patients were entered into two comparable groups of 288 patients after categorizing them as having multifocal/multicentric or unifocal breast cancers. Matching criteria were tumor size, grading, and hormone receptor status, which were equally distributed between both groups (P = 1.000 each). Disease free survival and the occurrence of relapse or of metastatic disease were evaluated. Cox's regression analysis was used for multivariate analysis. In the unifocal group, the mean breast cancer-specific survival time was 221.6 months as opposed to 203.3 months in the multicentric/multifocal group (P < 0.001, log-rank test). The occurrence of local relapse and distant metastasis was significantly increased in the multifocal group in comparison to the unifocal equivalent group (P < 0.001 and P < 0.003, respectively). Cox regression analysis for multivariate analyses demonstrated focality and centricity to be highly significant predictors for reduced overall survival (P = 0.016), local relapse (P = 0.001) and distant metastasis (P = 0.038). Tumor size, histopathological grading, hormone receptor status, and staging of lymph nodes are well-established prognostic parameters. Additionally, the number of foci should be considered as an independent prognostic parameter, which is currently not reflected in the TNM classification. We conclude that multicentric/multifocal BC is an independent BC risk factor and should be included in the risk assessment by re-evaluating the current TNM classification of the UICC.

We evaluated with long-term follow-up, the prognostic value of the mitotic activity index (MAI) and the volume corrected mitotic index (M/V-index) compared with that of the histological grade in breast cancer patients not treated with adjuvant systemic therapy. Of 739 consecutive patients living in the city of Nijmegen, the Netherlands, 477 patients with primary unilateral breast cancer were not treated with adjuvant systemic therapy and eligible for the study. In multivariate survival analyses the MAI and M/V-index showed similar hazard ratios (HRs) compared to HRs of histological grade for overall survival (OS) (HR: 1.45, 1.48, and grade II versus grade I (GII/GI) 1.34, grade III versus grade I (GIII/GI) 1.53, respectively) and for breast cancer specific survival (BCSS) (HR: 1.27, 1.57, and (GII/GI) 1.57 (GIII/GI) 2.32, respectively). Other independent prognostic variables for OS and BCSS were age at diagnosis, tumour size, and number of positive lymph nodes. In the present study with long term follow-up, we compared the prognostic value of mitotic activity with that of histological grade and found no advantage for the mitotic activity in predicting either BCSS or OS and concluded that histological grade and the mitotic activity were equally informative in predicting patient outcome. As histological grade is a well established and widely used prognosticator we do not have arguments to replace the histological grade by the mitotic indices MAI or M/V-index.

The present study was designed to assess the clinical characteristics and outcomes of metaplastic breast cancer (MBC) compared to general invasive ductal carcinoma (IDC) and the triple-negative subtype (TN-IDC). The study population included 35 MBC and 2,839 IDC patients, including 473 TN-IDC diagnoses, from the National Cancer Center, Korea between 2001 and 2008. The clinicopathological characteristics and clinical outcomes were retrospectively reviewed. Mean age of patients was 47.4 years for the MBC group and 48.3 years for the IDC group. The MBC patients presented with a larger tumor size (>/=T2, 74.3% vs. 38.8%, P < 0.001), more distant metastasis at the first diagnosis (8.6% vs. 2.0%, P = 0.04), higher histologic grade (grade 3, 65.7% vs. 41.4%, P < 0.001), fewer estrogen receptor (ER), and progesterone receptor (PgR) positivity (ER+, 5.7% vs. 65.4%, P < 0.001; PgR+, 8.6% vs. 55.8%, P < 0.001), higher Ki-67 expression (35.5 +/- 26.2% vs. 20.6 +/- 19.8%, P = 0.024), and more TN subtypes (80.0% vs. 16.7%, P < 0.001) compared to the IDC group. Fifteen (46.8%) MBC patients and 260 (9.3%) IDC patients experienced disease recurrence with a median follow-up of 47.2 months (range 4.9-100.6 months). MBC was a poor prognostic factor for disease recurrence and overall survival in univariate and multivariate analysis (HR 3.89 in recurrence, 95% CI: 1.36-11.14, P = 0.01; HR 5.29 in death, 95% CI: 2.15-13.01, P < 0.001). MBC patients also experienced more disease recurrence (HR 3.99, 95% CI: 1.31-12.19, P = 0.01) and poorer overall survival (HR 3.14, 95% CI: 1.19-8.29, P = 0.02) compared to the 473 TN-IDC patients, as reflected by aggressive pathological features. Patients with MBC appeared to have inherently aggressive tumor biology with poorer clinical outcomes than those with general IDC or TN-IDC.

Purpose: Promoter methylation of tumor suppressor genes in histologically negative sentinel lymph nodes (HNSN) of early stage breast cancer patients has not been extensively studied. This study evaluates the methylation frequency and pattern in HNSN to determine if detection of hypermethylation of one or more genes is associated with an increased recurrence risk in node negative breast cancer., Experimental Design: In 1998, a prospective study of patients with early stage breast cancer and HNSN was initiated in order to correlate sentinel node analysis with clinical outcome. Nodal tissue was selected from 120 HNSN patients for methylation analysis in at least one and up to six sentinel nodes using a panel of nine genes. Corresponding primary breast tumors from 79 patients were also evaluated for hypermethylation. Methylation analysis was performed using nested Methylation Sensitive PCR (n-MSP). Logistical regression was used to evaluate the relationship between clinical recurrence and methylation status., Results: Over a median follow-up of 79 months, 13 of the 120 patients had clinical recurrence. Hypermethylation of genes was frequently observed in HNSN, but there was no correlation of methylation pattern and clinical recurrence. However, increased frequency of gene methylation of the primary tumor correlated with clinical recurrence., Conclusions: Although hypermethylation of multiple genes occurs frequently in HNSN of breast cancer patients, it is not associated with breast cancer recurrence in the first 7 years of clinical follow-up.

Background: Pure mucinous breast carcinoma (PMBC) is a rare histologic type of mammary neoplasm. It has been associated with a better short-term prognosis than infiltrating ductal carcinoma (IDC) but identical long-term survival curves have been reported. The value of tumor size for TNM staging has been challenged because of the mucin content of the lesions. This study presents a large PMBC series with 20 years follow up as compared to IDC. The relative significance of a variety of common prognostic factors is calculated for this uncommon histology., Materials and Methods: A retrospective analysis of all PMBC cases reported in the SEER database between 1973 and 2002 was conducted. Overall survival (OS) and disease specific survival (DSS) were calculated at 5, 10, 15 and 20 years of follow up. Those curves were compared with all the IDC cases reported into the database during the same period. The prognostic significance of gender, race, laterality, age at diagnosis, T and N status, estrogen and progesterone receptors and administration of radiation therapy was calculated by univariate and multivariate analysis., Results: There were 11,422 PMBC patients reported. The median age at diagnosis was 71 years (Range 25-85). Fifty three percent of the tumors were well differentiated, 38% were moderately differentiated and the remaining 9% were poorly differentiated or anaplastic. The majority of the tumors were located in the upper outer quadrant (44%) the other 56% were roughly evenly divided between the upper inner, lower inner, lower outer and central quadrants. Eighty six percent of the patients had only localized disease at the time of surgery without nodal or distant disease while 12% had regional nodal involvement and 2% had distant metastases. The PMBC cases showed a better differentiation with lesions of lesser grade and more frequent ER/PR expression, smaller size and lesser nodal involvement when compared to the IDC cases of the same period. Kaplan Meier survival curves revealed a 5 years. breast cancer specific survival rate of 94%. Although slowly decreasing with time, 10, 15 and 20 years survival were 89%, 85% and 81% respectively compared to 82% (5 year), 72% (10 year), 66% (15 year) and 62% (20 year) for IDC. There were no significant differences in overall survival. Multivariate analysis by Cox regression revealed the nodal status (N) to be the most significant prognostic factor followed by age, tumor size (T), progesterone receptors and nuclear grade. Disease specific survival curves stratified for nodal status revealed a highly significant difference between node negative and node positive patients. The addition of radiation therapy after surgery did not significantly improve overall survival., Conclusions: This large retrospective comparative analysis confirms the less aggressive behavior of PMBC compared to IDC. This favorable outcome is maintained after 20 years. This tumor presents typically in older patients and is rarely associated with nodal disease. Positive nodal status appears to be the most significant predictor of worse prognosis.

Background: The Van Nuys Prognostic Index (VNPI) is a simple score for predicting the risk of local recurrence (LR) in patients with Ductal Carcinoma In Situ (DCIS) conservatively treated. This score combines three independent predictors of Local Recurrence. The VNPI has recently been updated with the addition of age as a fourth parameter into the scoring system (University of Southern California/ VNPI)., Patients and Methods: Our database consisted of 408 women with DCIS. Applying the USC/VNPI we reviewed retrospectively 259 patients who were treated with breast conserving surgery with or without radiotherapy (RT). Of these patients 63.5% had a low VNPI score, 32% intermediate and 4.5% a high score. In the low score group, the majority of the patients underwent Conservative Surgery (CS) without RT while in the intermediate group, almost half of the patients received RT. Eighty-three percent (83%) of the patients with high VNPI were treated with Conservative Surgery plus RT. Nodal assessment by Sentinel Lymph Node Biopsy was obtained in 32 patients since 2002., Results: Twenty-one Local Recurrences were observed (8%) with a mean follow up of 130 months: sixteen were invasive. No statistically significant differences in Disease Free Survival were reached in all groups of VNPI score between patients treated with Conservative Surgery or Conservative Surgery plus RT. However it was noted that the higher the VNPI score, the lower was the risk of local recurrence in the group treated additionally with RT, even though it was not statistically significant. Further analysis included those patients treated with Conservative Surgery alone and followed up. Disease-free survival (DFS) at 10 years was 94% with low VNPI and 83% in both intermediate and high score (P < 0.05). No significant differences were observed in the subgroups of VNPI. The Local Relapse rate after Conservative Surgery alone, increased with tumor size, margin width, and pathology classification (P < 0,05), while age was not found to be a significant factor. Lesions with only mammographic appearances are associated with lower DFS but it did not reach significance (P = ns), while assumption of estrogenic hormones and familial history of breast cancer are significant factors associated with a higher risk of local recurrence. After multivariate analysis including seven clinical and pathological factors, the only significant predictors of local recurrence remained margin width of surgical excision, previous therapy with estrogens (contraceptives or Hormone Replacement Therapy) and the Van Nuys pathologic classification. The overall survival breast cancer specific was 99% and no differences were observed between groups (P = ns). The comparison of patients treated with a total mastectomy and those conservatively treated showed a significantly better local relapse free survival rate obtained with mastectomy (98.2% vs. 89.7% at 10 years P = 0.02). However, the overall cause-specific survival did not prove any better outcome (98.7% in both groups). Of the 32 patients who underwent a Sentinel Lymph Node Biopsy, four were found to have micrometastases and all of them had a previous Directional Vacuum Assisted Biopsy., Conclusions: Although in our series there is not a significant difference in LR rates by the parameter of age, the new USC/VNPI is still a simple and reliable scoring system for therapeutic management of DCIS. We did not find any statistically significant advantage in groups treated with the addition of RT. Obtaining wide surgical margins appears to be the strongest prognostic factor for local recurrence, regardless of other pathological factors or the addition of adjuvant radiation therapy. However, only prospective randomized studies can precisely predict the risk of LR of conservatively treated DCIS. The clinical significance of Sentinel Lymph Nodes micrometastases Immuno-Histo-Chemistry-detected found in DCIS patients remains uncertain. However, we hypothesize that the anatomical disruption after preoperative biopsy procedures increases the likelihood of epithelial cell displacement and the frequency of IHC-positive Sentinel Lymph Nodes, both of which are directly proportional to the degree of manipulation.

This study examined whether psychological distress in newly diagnosed breast cancer patients was associated with their survival. We analyzed data from 1,588 breast cancer patients who filled in the EORTC QLQ-C30 questionnaire and the Hospital Anxiety and Depression Scale (HADS) 2 months after their primary operation. The median follow-up time was 12.9 years. Psychological distress (EORTC QLQ-C30 emotional function; HADS anxiety; HADS depression) and EORTC fatigue, physical function, and overall ratings were used to predict recurrence-free and overall survival, controlling for the known clinical and histopathological prognostic factors (biological model) using Cox multivariate regression analysis. Low levels of psychological distress (good EORTC emotional function) and low fatigue independently predicted longer recurrence-free and overall survival, controlling for biological factors. Lack of anxiety (HADS) also predicted longer recurrence-free survival. When added in combination to the biological model, fatigue remained a significant predictor of recurrence-free survival (P = 0.0004; risk ratio 1.32 (1.13-1.54)) and emotional function remained a significant predictor of overall survival (P = 0.0074; risk ratio 0.81 (0.70-0.95)). Low psychological distress and a low level of fatigue may cause a greater cancer resistance or may reflect underlying mental and physical robustness.

This study aims to examine the incidence and risk factors of bilateral breast cancer in area with low incidence rate. A total of 120 and 1902 women with bilateral and unilateral breast cancers were enrolled; various factors, including those concerning their medical history and life style, were extracted. Using Kaplan-Meier method, we calculate the cumulative incidence of contralateral breast cancer. The results show as follows. The cumulative incidences of contralateral breast cancer at 1, 3, 5 years after diagnosis of first breast cancer were 1.15, 1.94, and 2.97%, respectively. The statistically significant risk factors included menopause (Hazard Ratio (HR) =1.56, (1.00-2.42)), invasive lobular carcinoma (HR=2.98, (1.35-6.56)), receiving chemotherapy (HR=2.21, (1.43-3.42)) and/or radiotherapy (HR=3.32, (2.19-5.05) and a protective factor was tamoxifen therapy (HR=0.5 (0.34-0.74). Size of the second occurred tumour (2.97 cm) tended to be smaller than the first one (3.58 cm) with borderline statistical significance (p=0.0731). Comparing to the existing data on Western countries, we find a higher risk for developing contralateral breast cancer in Taiwan where a low incidence of first breast cancer rate with early age diagnosis is noted. It suggests that first primary breast tumour with early age of onset and lobular carcinoma are found more likely to develop bilateral breast cancers.

The presence of cytokeratin-positive cells in the bone marrow of breast cancer patients has been proven to be an independent prognostic factor. Their fate in primary breast cancer patients undergoing adjuvant therapy is of particular interest. We investigated the bone marrow status of 112 patients undergoing postoperative adjuvant treatment before and after therapy. A total of 373 patients with histologically confirmed primary breast cancer underwent bone marrow aspiration at the time of primary surgery. All patients were informed of their bone marrow status and offered repeat aspiration after 12 months. All patients were then treated with adjuvant chemotherapy, endocrine therapy or both based on current treatment recommendations. About 112 patients returned for a second bone marrow aspiration after a mean interval of 12 months following the initiation of adjuvant treatment. In 93 of 112 patients (83%) disseminated tumor cells had been found in the bone marrow before initiation of systemic chemo/endocrine therapy. At the time of follow-up sampling, after surgery and completion of adjuvant chemotherapy, the positivity rate dropped to 24%. Positive bone marrow status during follow-up was only associated with grading (p=0.020). Adjuvant treatment regimens are not able to completely eliminate cytokeratin-positive cells from the bone marrow. Prospective studies need to evaluate, whether these cells could become targets for additional adjuvant therapy.

The phosphatidylinositol-3-kinase (PI3K)-AKT signaling pathway is considered to play an important role in tumorigenesis. Frequent somatic mutations in the PI3K subunit p110alpha (PIK3CA) occur in a variety of cancer types. We screened 250 primary human breast tumors for mutations in PIK3CA in order to determine associations with pathological features and with patient outcome. The frequency of PIK3CA mutations in the C2, helical and kinase domains was 35% (88/250). Mutations were associated with larger tumor size (p = 0.004) and positive estrogen receptor status (p = 0.008). Patients with PIK3CA mutations showed significantly worse survival (p = 0.004), particularly those with positive estrogen receptor expression or non-amplified erbB2 (both p = 0.002). PIK3CA mutation was an independent factor for worse survival in breast cancer patients with non-amplified erbB2 (RR = 2.6, 95%CI [1.2-5.5], p = 0.016).

Background: The Trefoil Factor 1 (TFF1/pS2), a peptide consisting of 60 amino acids, is the most abundant estrogen-induced messenger RNA present in MCF-7 breast cancer cells. The objective of this work was to evaluate the cytosolic TFF1 content in breast carcinomas, its possible relationship with different clinical-pathological parameters, and its potential prognostic significance and predictive value., Methods: Cytosolic TFF1 levels were examined by immunoradiometric assay in 1031 patients with invasive breast cancer. The median follow-up period was of 50 months., Results: There was a wide variability of cytosolic TFF1 levels in tumors (0.9-743.2 ng/mg protein). Statistical analysis showed that TFF1 levels were significantly higher in premenopausal patients (p = 0.001), as well as in tumors showing any of the following characteristics: good differentiation (p = 0.0001), ER and PgR positivity (p = 0.0001 and p = 0.001, respectively), diploidy (p = 0.045) and a high S-phase fraction (p = 0.001). In addition, the presence of high intratumoral TFF1 levels (cut-off: 2 ng/mg protein) was independently associated with a shorter overall survival in the group of patients as a whole (p = 0.001) as well as in the subgroup with node-negative breast cancer (p = 0.0004). Likewise, high intratumoral TFF1 levels were associated with a more prolonged overall survival in patients who received adjuvant tamoxifen (p = 0.004)., Conclusions: In breast cancer patients, intratumoral TFF1 levels are associated with a better clinical outcome, especially in those with node-negative tumors. In addition, TFF1 levels have a low but significant predictive value in regards to response to adjuvant therapy with tamoxifen.

Background: The prognosis of patients with liver metastases from breast cancer is commonly poor. After initial diagnosis of hepatic metastases, a median survival time of 1-20 months can be expected. The definition of prognostic factors for such patients may influence therapeutic decisions. In particular, the characterization of patients who can expect long-term survival could assist in optimizing treatment., Methods: We retrospectively studied n = 350 patients with liver metastases from breast cancer. All patients were stratified following their survival after occurrence of liver metastases. Kaplan-Meier studies were performed, as well as univariate and multivariate analyses of several clinical, histopathological and therapeutic factors., Results: Median survival time was 14 months. N = 66 (18.9%) patients survived longer than 36 months after the primary diagnosis. Multivariate analysis showed prognostic relevance for the time interval between the primary diagnosis of breast cancer and the initial diagnosis of hepatic metastases (p < 0.05). Furthermore, prognostic relevance was found for the pattern of metastasization (p < 0.05) and for signs of hepatic dysfunction (ascites, jaundice, p < 0.005). Univariate analysis showed a prognostic benefit for patients with an expression of Ki-67 < 20%, p53 < 50% and a positive hormonal receptor status. Patients who received a regional therapy survived on average longer than patients who were only treated systemically (33 versus 11 months, p < 0.001)., Conclusions: Consideration of prognostic implications of the described parameters may help to find the most appropriate treatment for patients with liver metastases from breast cancer. The possibility of local therapeutic interventions should be considered in a defined subgroup.

Background: Despite the approximate 42,000 yearly new cases of breast cancer in France, there have been very few exhaustive studies on the clinicopathological features and treatment options of this disease., Methods: Thus, a prospective, non-selective, nationwide survey on infiltrating breast cancer (IBC) was conducted in France from September 2001 to April 2002, in order to assess the epidemiological features of newly diagnosed disease, the prognostic and predictive variables with a special emphasis on hormone receptors, and the current approaches to therapy in everyday clinical practice., Results: In total, 1159 patients were evaluable (median age 57 years); two-thirds of women were postmenopausal and 38% had undergone hormonal replacement therapy (HRT). Ductal and lobular infiltrating cancers represented 82.3% and 11.6% of cases, respectively. Most tumours expressed oestrogen (79.7%) and progesterone (69.7%) receptors. Overexpression of the human epidermal growth factor receptor-2 oncogene was found in 20.6% of the assessed cases. IBC diagnosed in women under HRT presented significantly better clinico-pathological features than in non-users. All patients underwent surgery as first treatment: 77.5% breast-conserving surgery (BCS) and 22.5% mastectomy; 1024 patients also underwent axillary surgery. The overall axillary lymph-node involvement rate was 44.4%. Radiotherapy was proposed in 98% and 83% of the women who had undergone BCS and mastectomy, respectively. Adjuvant chemotherapy was delivered in 58.7% of patients and hormonal treatment was provided in 76.5% of patients; tamoxifen was the most widely used hormonal treatment., Conclusions: This study showed a trend for global downstaging of IBC (with favourable clinico-pathological features), leading to a high rate of BCS. Postoperative treatments were widely used, in accordance with national and international guidelines. Use of aromatase inhibitors and taxanes was limited, but is likely to rise in the future.

One of the more problematic and dreaded complications of breast cancer is lymphoedema. Our objective was to determine the prevalence of lymphoedema 6-months following breast cancer treatment and to examine potential risk factors among a population-based sample of women residing in South-East Queensland (n = 176). Women were defined as having lymphoedema if the difference between the sum of arm circumferences (SOAC) of the treated and untreated sides was >5 cm (prevalence = 11.9%) or >10% (prevalence = 0.6%), their multi- frequency bioelectrical impedance (MFBIA) score was > or =3 standard deviations above the reference impedance score (prevalence = 11.4%), or they reported 'yes' when asked if arm swelling had been present in the previous 6 months (prevalence = 27.8%). Of those with lymphoedema defined by MFBIA, only 35% were detected using the SOAC method (difference > 5 cm), while 65% were identified via the self-report method (i.e., respective sensitivities). Specificities for SOAC (difference > 5 cm) and self-report were 88.5% and 76.9%, respectively. When examining associations between presence of lymphoedema and a range of characteristics, findings also varied depending on the method used to assess lymphoedema. Nevertheless, one of the more novel and significant findings was that being treated on the non-dominant, compared to dominant, side was associated with an 80% increased risk of having lymphoedema (MFBIA). Our work raises questions about the use of circumferences as the choice of measurement for lymphoedema in both research and clinical settings, and assesses MFBIA as a potential alternative.