Impact of autoimmune diseases on outcome of patients with early breast cancer.

Our aim was to analyze the impact of a concurrent autoimmune disease on outcome of patients with early breast cancer. We reviewed medical charts of patients with a diagnosis of autoimmune diseases (AD) among a population of 17.153 cases. We categorized ADs as endocrine, rheumatic, systemic, neurological diseases and vasculitis. For each patient in the study group, we matched 2 patients. The events to determine overall survival (OS) and disease free survival (DFS) were identified from follow-up data. We identified 279 (1.62%) patients with early breast cancer and concurrent ADs. The median follow-up was 7.0 years. The 10-year OS rate was 86% (95% CI, 80% to 91%) in the study group and 90% (95% CI, 86% to 93%) for the control group (p = 0.011). In patients with ER positive/HER2 negative subtype a worse OS was observed in the study group when compared to the control group (p = 0.0046); this difference remained statistically significant when the analysis was restricted to breast cancer mortality (p = 0.045). The 10-year DFS rate was 69% (95% CI, 61% to 76%) in the study group and 72% (95% CI, 66% to 77%) for the control group (p = 0.22). Autoimmunity at diagnosis of early breast cancer is associated with worse survival.

Outcome and Medial Presentation of Breast Cancer: European Institute of Oncology Experience.

BACKGROUND: No analyses have investigated the prognostic role of medial presentation in breast cancer patients on disease-free survival (DFS) and overall survival according to immunohistochemically-defined subtypes. PATIENTS AND METHODS: We collected information from the institutional clinical database on consecutive breast cancer patients who underwent conservative surgery at the European Institute of Oncology, Milan, Italy, between 1994 and 2008. We compared the outcomes of patients with medial breast cancer with those of patients with nonmedial tumors observed at the institution during the same period. RESULTS: Among 7369 evaluable patients, 2254 (24%) had their primary tumors in medial quadrants and 7015 (76%) in other areas. Five-year DFS was 84.7% and 86.6% (P = .008) in patients with medial and nonmedial disease, respectively. In multivariate analysis, medial location was correlated with greater risk of recurrence (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.11-1.35; P < .0001) and death (HR, 1.27; 95% CI, 1.09-1.49; P = .0028). CONCLUSION: Medial presentation is an adverse prognostic factor for breast cancer patients.

Outcomes of patients with breast cancer who present with ipsilateral supraclavicular or internal mammary lymph node metastases.

BACKGROUND: The prognostic implications of internal mammary (IM) and supraclavicular (SC) node involvement in locally advanced breast cancer is still unclear. PATIENTS AND METHODS: We evaluated 107 patients with IM (n = 65) or SC (n = 42) node involvement who underwent operation at the European Institute of Oncology between 1997 and 2009 to assess their prognostic features. We subsequently analyzed matched cohorts, using the 107 patients as cases and another group of patients as a control cohort, to evaluate prognostic differences between patients with and those without IM or SC node involvement. RESULTS: Five-year disease-free survival (DFS) was 84% in IM vs. 38.8% in SC node involvement (P < .0001), and 5-year overall survival (OS) was 96.9% in IM node vs. 57.1% in SC node involvement (P < .0001). No difference in outcome was found between patients with and controls without IM node involvement. Conversely, a statistically significant difference in DFS and locoregional recurrence was observed in patients with SC node involvement compared with controls without SC node involvement. CONCLUSION: SC node involvement correlated with a significantly poorer outcome in patients with locally advanced breast cancer. Adequate staging, including biopsy of suspicious locoregional ipsilateral lymph nodes, is mandatory in these patients. Patients with IM or SC node involvement should be treated with curative intent using combined-modality treatments.

Therapeutic effect of ß-blockers in triple-negative breast cancer postmenopausal women.

Beta-blockers (BB) drugs have been used for decades worldwide, mainly to treat hypertension. However, in recent epidemiological studies, BBs were suggested to improve cancer prognosis. In the wake of this evidence, we evaluated the possible therapeutic effect of BBs in triple-negative breast cancer (TNBC) patients. We identified 800 postmenopausal women operated between 1997 and 2008 for early primary TNBC. The effect of BB intake on the risk of breast cancer (BC) recurrence and death was evaluated through competing risk and Cox regression survival models. At cancer diagnosis, 74 (9.3 %) women out of 800 were BBs users. Median age was 62 years in BB users and 59 years in non-users (P = 0.02). BB users and non-users were similarly distributed by all tumor characteristics. The 5-year cumulative incidence of BC-related events was 13.6 % in BB users and 27.9 % in non-users (P = 0.02). The beneficial impact of BBs remained statistically significant at multivariable analysis (HR, 0.52; 95 % CI 0.28-0.97), after the adjustment for age, tumor stage, and treatment, peritumoral vascular invasion and use of other antihypertensive drugs, antithrombotics, and statins. Adjusted HRs for metastases and for BC deaths were 0.32 (95 % CI 0.12-0.90) and 0.42 (95 % CI 0.18-0.97), respectively, in favor of BBs. Hypertension, other antihypertensive drugs, antithrombotics, and statins did not impact prognosis. In this series of postmenopausal TNBC patients, BB intake was associated with a significantly decreased risk of BC-related recurrence, metastasis, and BC death. Innovative therapeutic strategies including BBs should be urgently explored in cancer patients.

Methylenetetrahydrofolate reductase (MTHFR) and breast cancer risk: a nested-case-control study and a pooled meta-analysis.

BACKGROUND: A reduced activity of methylenetetrahydrofolate reductase (MTHFR) due to frequent C677T polymorphism affects DNA synthesis, repair and methylation and may be implicated in breast cancer risk. METHODS: We conducted a nested case-control study within a phase III prevention trial of tamoxifen. After a median follow-up of 81.2 months, 79 of the 5,408 hysterectomised women aged 35-70 years, who had received either tamoxifen 20 mg/day or placebo for 5 years, developed breast cancer. A total of 46 breast cancer cases and 80 unaffected controls matched to treatment allocation, years from randomization (+/-2 years) and age at randomization (+/-5 years), underwent genotyping for MTHFR C677T polymorphism using real time PCR. RESULTS: The MTHFR 677 genotype frequencies for CC, CT, TT in breast cancer cases were 30%, 44% and 26%, respectively, and 35%, 51%, 14% in controls. We observed a borderline significant odds ratio of 2.51 (95% CI, 0.96-6.55) of breast cancer in subjects with 677TT genotype, with no further association after stratifying for age and treatment group. A meta-analysis of 18 studies, including our own, showed an increased risk of breast cancer in premenopausal women with 677TT genotype, with an odds ratio of 1.42 (95% CI, 1.02-1.98). CONCLUSIONS: Our study lends support to a positive association between the MTHFR variant homozygous allele 677TT and breast cancer risk. Additional studies are warranted to provide further insight into the role of folate metabolism deficiency and breast cancer.