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Background: Tumor-infiltrating lymphocytes (TILs) are a robust prognostic adjunct in invasive breast cancer, but their clinical role in ductal carcinoma in situ (DCIS) has not been ascertained., Patients and Methods: We evaluated the prevalence and clinical relevance of TILs in a well annotated series of 1488 consecutive DCIS women with a median follow-up of 8.2 years. Detailed criteria for TILs evaluation were pre-defined involving the International Immuno-Oncology Biomarker Working Group. TILs percentage was considered both as a continuous and categorical variable. Levels of TILs were examined for their associations with ipsilateral breast event (IBE), whether in situ or invasive., Results: Of the 1488 patients with DCIS under study, 35.1% had <1%, 58.3% 1-49% and 6.5% ≥50% peri-ductal stromal lymphocytes. The interobserver agreement in TILs evaluation, measured by the intraclass correlation coefficient (ICC) was 0.96 (95% CI 0.95-0.97). At univariable analysis, clinical factors significantly associated with TILs (P ≤0.001) were intrinsic subtype, grade, necrosis, type of surgery. Her-2 positive DCIS were more frequently associated with TILs (24% of patients with TILs ≥50%), followed by the triple negative (11%), Luminal B/Her-2 positive (9%) and Luminal A/B subtypes (1%) (P < 0.0001). We did not find any association between TILs as a continuous variable and the risk of IBEs. Likewise, when patients were stratified by TILs percentage (<1%, between 1% and 49.9%, and ≥50%), no statistically significant association was observed (10-year cumulative incidence of IBEs: 19%, 17.3%, and 18.7% respectively, P = 0.767)., Conclusion: TILs occur more frequently in the Her-2 positive DCIS. Although we did not find a significant association between TILs and the 10-year risk of IBE, our data suggest that immunotherapies might be considered in subsets of DCIS patients., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Although tumor-infiltrating lymphocytes (TILs) have been associated with a favorable prognosis in triple-negative breast cancer (TNBC) patients, this marker is not currently considered robust enough for entering the clinical practice. In the present study, we assessed the clinical validity of the guidelines recently issued by the International TIL Working Group in a large retrospective series of well-annotated TNBC patients., Patients and Methods: TILs were evaluated in all the full-face H&E sections from 897 consecutive TNBC (i.e. tumors with <1% of ER and PgR immunoreactivity and absence of HER2 overexpression or amplification) patients diagnosed and treated at the European Institute of Oncology between 1995 and 2010 (median follow-up 8.2 years, range 6 months to 18 years). All mononuclear cells were evaluated in the stromal area within the borders of the invasive tumor, reported as a percentage value and treated as a continuous variable in survival analysis., Results: The median percentage of TILs was 20%, and 21.9% of the cases had ≥50% (lymphocyte predominant breast cancer, LPBC) TILs. At univariable survival analysis, TILs were a significant predictor of better disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) (P < 0.0001). Multivariable analysis confirmed that each 10% increase in TILs strongly predicted better survival, independent of patients' age, lymph node status, tumor size, histological grade, peritumoral vascular invasion and Ki-67 labeling index. Patients with LPBC had a 10-year survival rate of 71%, 84% and 96% for DFS, DDFS and OS, respectively. Stratified analysis revealed a positive correlation between TILs and OS across all the subgroups analyzed., Conclusion: Our data support the analytical validity of the recently issued TILs evaluation guidelines in the clinical practice., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Limited data are available on the prognostic value of changes in the biological features of residual tumours following neoadjuvant therapies in breast cancer patients., Patients and Methods: We collected information through the institutional clinical database on all consecutive breast cancer patients treated with neoadjuvant chemotherapy at the European Institute of Oncology (IEO), Milan, Italy, between 1999 and 2011. We selected patients who did not achieve pathological complete response at final surgery. All patients had a pathological evaluation, including ER, PgR, HER2 protein and Ki-67 expression carried out at the IEO both at diagnostic core biopsy and at final surgery., Results: We identified a total of 904 patients. The 5% of patients who were ER positive at diagnostic biopsy had ER-negative residual tumour at final surgery. For PgR expression, 67% of the patients, whose tumours had a PgR >20% at diagnostic biopsy had a PgR <20% at final surgery. The Ki-67 expression changed from >20% to <20% in 40% of the patients. At the multivariate analysis, the decrease of PgR-immunoreactive cells correlated with improved outcome in terms of disease-free survival (DFS) [hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.54-1.00, P 0.046]. In addition, the decrease of Ki-67 expression to <20% of the cells at final surgery was found to be associated with better outcome both in terms of DFS (HR 0.52; 95% CI 0.40-0.68 P < 0.0001) and overall survival (HR 0.45; 95% CI 0.32-0.64, P < 0.0001)., Conclusion: The decrease of PgR and Ki-67 expression after preoperative chemotherapy has a prognostic role in breast cancer patients with residual disease., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Despite several studies support a positive association between heavy alcohol consumption and liver cancer risk, a consistent dose-risk relationship has not yet been established. We carried out a systematic review and a meta-analysis of the association between alcohol intake and liver cancer occurrence, following the Meta-analysis Of Observational Studies in Epidemiology guidelines. We searched for cohort and nested case-control studies on the general population published before April 2013, using PubMed and EMBASE. Summary meta-analytic relative risks (RRs) were estimated using random-effect models. We included 16 articles (19 cohorts) for a total of 4445 incident cases and 5550 deaths from liver cancer. Compared with non-drinking, the pooled RRs were 0.91 (95% confidence interval, CI, 0.81-1.02) for moderate drinking (< 3 drinks per day) and 1.16 (95% CI, 1.01-1.34) for heavy drinking (≥ 3 drinks per day), with significant heterogeneity among studies. The dose-risk curve suggested a linear relationship with increasing alcohol intake in drinkers, with estimated excess risk of 46% for 50 g of ethanol per day and 66% for 100 g per day. This systematic review suggests a moderate detrimental role of consumption of 3 or more alcoholic drinks per day on liver cancer, and a lack of association with moderate drinking. Our results have to be taken with due caution on account of the possible limitations of the original studies included in the meta-analysis., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Postsurgical treatment of ductal intraepithelial neoplasia (DIN) with standard doses of tamoxifen has not reached a consensus yet. Given positive results of low-dose tamoxifen on breast cancer biomarkers modulation, we analyzed a large cohort of DIN patients treated with low-dose tamoxifen or no treatment as per institutional guidelines., Patients and Methods: All consecutive women operated on at the European Institute of Oncology for estrogen receptor (ER)-positive DIN (474 treated with low-dose tamoxifen and 509 untreated patients) were followed up for a median of 7 years., Results: Compared with untreated patients, a significant 30% reduction in breast cancer risk was observed on low-dose tamoxifen with an adjusted hazard ratio (HR) = 0.70 [95% confidence interval (CI) 0.51-0.94], with a greater benefit in postmenopausal (HR = 0.57; 95% CI 0.34-0.94) than in premenopausal women (HR = 0.79; 95% CI 0.54-1.17). Treated patients with ER and progesterone receptor (PgR) >50% DIN had a lower incidence of breast events than untreated ones (HR = 0.61; 95% CI 0.40-0.94), whereas no protective effect has been observed in patients with ER or PgR <50% DIN. Drug discontinuation resulted in a doubled risk of recurrence in premenopausal women only (HR = 1.95; 95% CI 0.98-3.89). No excess of endometrial cancer occurred., Conclusions: Low-dose tamoxifen is a promising and safe strategy for highly endocrine responsive DIN. Treatment adherence is crucial in premenopausal women. A definitive trial is ongoing.

Background: There is convincing evidence that alcohol consumption increases the risk of cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx. Most of the data derive from studies that focused on the effect of moderate/high alcohol intakes, while little is known about light alcohol drinking (up to 1 drink/day)., Patients and Methods: We evaluated the association between light drinking and cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx, through a meta-analytic approach. We searched epidemiological studies using PubMed, ISI Web of Science and EMBASE, published before December 2010., Results: We included 222 articles comprising ∼92 000 light drinkers and 60 000 non-drinkers with cancer. Light drinking was associated with the risk of oropharyngeal cancer [relative risk, RR = 1.17; 95% confidence interval (CI) 1.06-1.29], esophageal squamous cell carcinoma (SCC) (RR = 1.30; 95% CI 1.09-1.56) and female breast cancer (RR = 1.05; 95% CI 1.02-1.08). We estimated that ∼5000 deaths from oropharyngeal cancer, 24 000 from esophageal SCC and 5000 from breast cancer were attributable to light drinking in 2004 worldwide. No association was found for colorectum, liver and larynx tumors., Conclusions: Light drinking increases the risk of cancer of oral cavity and pharynx, esophagus and female breast.

Background: Alcohol is capable of traversing the blood-brain barrier and is thus a possible risk factor for brain cancer. Several epidemiological studies have been published on the issue, a number of those during recent years, with inconsistent findings., Materials and Methods: We performed a systematic literature search in the Medline and EMBASE databases. We found a total of 19 studies providing risk estimates for total alcohol or specific alcoholic beverages. Pooled estimates of the relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects models., Results: The pooled RR of brain cancer for alcohol drinkers versus non-drinkers was 0.97 (95% CI 0.82-1.15; based on 12 studies). Moderate (<2 drinks/day) and heavy alcohol drinkers had RRs of 1.01 (95% CI 0.81-1.25) and 1.35 (95% CI 0.85-2.15), respectively. With reference to specific alcoholic beverages, the RRs were 1.01 (95% CI 0.70-1.48) for wine, 0.96 (95% CI 0.82-1.12) for beer, and 1.20 (95% CI 1.01-1.42) for spirit consumption. The RRs for drinkers versus non-drinkers were 0.93 (95% CI 0.81-1.07) for glioma and 0.71 (95% CI 0.45-1.12) for meningioma., Conclusions: Alcohol drinking does not appear to be associated with adult brain cancer, though a potential effect of high doses deserves further study.

Background: Whether an association between alcohol drinking and non-Hodgkin lymphoma (NHL) risk exists is an open question. In order to provide quantification of the issue, we carried out a meta-analysis of published data., Methods: We identified 21 case-control and 8 cohort studies, including a total of 18,759 NHL cases. We derived meta-analytic estimates using random-effects models, taking into account correlation between estimates., Results: The overall relative risk (RR) of NHL for drinkers versus non-drinkers was 0.85 [95% confidence interval (CI) 0.79-0.91]. Compared with non-drinkers, the pooled RRs were 0.88 for light (≤1 drink per day), 0.87 for moderate (1 to <4 drinks per day), and 0.84 for heavy (≥4 drinks per day) alcohol drinking. There was no association for light drinkers in cohort studies, whereas for moderate and heavy drinkers, the RRs were similar in case-control (0.85 for moderate, 0.92 for heavy) and cohort (0.89 for moderate, 0.79 for heavy) studies. The inverse relation with alcohol consumption (drinkers versus non-drinkers) was similar in men (RR = 0.83) and women (RR = 0.86), but apparently stronger in studies from Asia (RR = 0.69) than other world areas (RR = 0.88)., Conclusion: This meta-analysis provides quantitative evidence of a favourable role of alcohol drinking on NHL risk, though the lack of a biological explanation suggests caution in the interpretation of results.

Background: The role of alcohol consumption in relation with renal cell carcinoma is still unclear; a few studies have reported a beneficial effect of moderate levels of alcohol consumption, whereas it remains still under debate whether there is a dose-response association., Materials and Methods: Twenty observational studies (4 cohort, 1 pooled and 15 case-control) reporting results on at least three levels of alcohol consumption were selected through a combined search with PubMed and EMBASE of articles published before November 2010. Overall relative risks (RRs) and 95% confidence intervals (CIs) were estimated using random-effects models, and both second-order fractional polynomials and random effect meta-regression models were implemented for the study of dose-risk relation., Results: The estimated RRs were 0.85 (95% CI: 0.80-0.92) for any alcohol drinking, 0.90 (95% CI: 0.83-0.97) for light drinking (0.01-12.49 g/day), 0.79 (95% CI: 0.71-0.88) for moderate drinking (12.5-49.9 g/day) and 0.89 (95% CI: 0.58-1.39) for heavy drinking (≥50 g/day), respectively., Conclusion: Our meta-analysis supports the hypothesis of a negative effect of moderate alcohol consumption on the risk of renal cell cancer.

Background: We aimed at investigating the risk of bladder cancer at different levels of alcohol consumption by conducting a meta-analysis of epidemiological studies., Patients and Methods: In October 2010, we carried out a systematic literature search in the Medline database, using PubMed. We identified 16 case-control and 3 cohort studies, including a total of 11 219 cases of bladder cancer, satisfying the inclusion criteria for this meta-analysis. Moderate alcohol intake was defined as <3 drinks per day (i.e. <37.5 g of ethanol per day) and heavy intake as ≥3 drinks/day. Pooled estimates of the relative risks (RR) and the corresponding 95% confidence intervals (CI) were calculated using random effects models., Results: Compared with non-drinkers, the pooled RRs of bladder cancer were 1.00 (95% CI 0.92-1.09) for moderate and 1.02 (95% CI 0.78-1.33) for heavy alcohol drinkers. When we excluded four studies that did not adjust for tobacco smoking, the corresponding estimates were 0.98 (95% CI 0.89-1.07) and 0.97 (95% CI 0.72-1.31)., Conclusions: This meta-analysis of epidemiological studies provides definite evidence on the absence of any material association between alcohol drinking and bladder cancer risk, even at high levels of consumption.

Background: In order to provide a precise quantification of the association between alcohol drinking and esophageal and gastric cardia adenocarcinoma risk, we conducted a meta-analysis of available data., Patients and Methods: We identified 20 case-control and 4 cohort studies, including a total of 5500 cases. We derived meta-analytic estimates using random-effects models, taking into account correlation between estimates, and we carried out a dose-risk analysis using nonlinear random-effects meta-regression models., Results: The relative risk (RR) for drinkers versus nondrinkers was 0.96 [95% confidence interval (CI) 0.85-1.09] overall, 0.87 (95% CI 0.74-1.01) for esophageal adenocarcinoma and 0.89 (95% CI 0.76-1.03) for gastric cardia adenocarcinoma. Compared with nondrinkers, the pooled RRs were 0.86 for light (≤ 1 drink per day), 0.90 for moderate (1 to < 4 drinks per day), and 1.16 for heavy (≥ 4 drinks per day) alcohol drinking. The dose-risk model found a minimum at 25 g/day, and the curve was < 1 up to 70 g/day., Conclusions: This meta-analysis provides definite evidence of an absence of association between alcohol drinking and esophageal and gastric cardia adenocarcinoma risk, even at higher doses of consumption.

Background: To evaluate the outcome of breast cancer patients after locoregional recurrence (LRR) according to tumor biological features evaluated at first diagnosis and at the time of recurrence., Patients and Methods: We collected information on all consecutive breast cancer patients operated at the European Institute of Oncology between 1994 and 2005. The tumor characteristics and subsequent outcome of patients who experienced LRR were analyzed., Results: Two hundred and seventy nine patients with LRR were identified, 197 and 82 patients with local and regional recurrence respectively. The overall discordance rate between primary cancer and LRR was 9% for estrogen receptor expression, 22% for progesterone receptor and 4% for human epidermal growth factor receptor 2. For patients with regional recurrence, the risk of distant metastasis was significantly higher compared with local relapse in case of late recurrence (hazard ratio [HR] = 2.76; 95% CI 1.31-5.85). Patients with triple-negative breast cancer at LRR experienced a higher risk of subsequent relapse (HR 2.87 [1.67-4.91]) and death (HR 2.00 [1.25-3.19])., Conclusion: LRR correlates with a high risk of subsequent events and death in particular in patients with triple-negative subtype.

Background: Whether an association between alcohol drinking and gastric cancer risk exists is an open question. In order to provide a definite quantification of the association between alcohol drinking and gastric cancer risk, we conducted a meta-analysis of available data., Patients and Methods: We carried out a PubMed search of articles published up to June 2010 and identified 44 case-control and 15 cohort studies, including a total of 34 557 gastric cancer cases. We derived meta-analytic estimates using random-effects models, taking into account correlation between estimates. We carried out a dose-risk analysis using nonlinear random-effects meta-regression models., Results: Compared with nondrinkers, the pooled relative risk (RR) was 1.07 [95% confidence interval (CI) 1.01-1.13] for alcohol drinkers and 1.20 (95% CI 1.01-1.44) for heavy alcohol drinkers (≥4 drinks per day). The pooled estimates were apparently higher for gastric noncardia (RR for heavy drinkers=1.17, 95% CI 0.78-1.75) than for gastric cardia (RR=0.99, 95% CI 0.67-1.47) adenocarcinoma. The dose-risk model estimated a RR of 0.95 (95% CI 0.91-0.99) for 10 g/day and 1.14 (95% CI 1.08-1.21) for 50 g/day., Conclusions: This meta-analysis provides definite evidence of a lack of association between moderate alcohol drinking and gastric cancer risk. There was, however, a positive association with heavy alcohol drinking.

Background: The role of alcohol consumption as an independent risk factor for lung cancer is controversial. Since drinking and smoking are strongly associated, residual confounding by smoking may bias the estimation of alcohol consumption and lung cancer risk relation. Therefore, we undertook a meta-analysis to quantitatively assess the association between alcohol and risk of lung cancer in never smokers., Methods: After a literature search in Medline, we included all case-control and cohort studies published up to January 2010 that reported an estimate of the association between alcohol intake and lung cancer risk in never smokers., Results: We selected 10 articles, including 1913 never smoker lung cancer cases. The random-effects pooled relative risk (RR) for drinkers versus nondrinkers was 1.21 [95% confidence interval (CI) 0.95-1.55]. The same figure was 1.05 (95% CI 0.89-1.23) after the exclusion of one outlier study. At the dose-response analysis, RR for an increase in alcohol intake of 10 g/day was 1.01 (95% CI 0.92-1.10)., Conclusions: Alcohol consumption was not associated with lung cancer risk in never smokers. Even if the synergistic effect of smoking and alcohol cannot be ruled out, our results suggest that alcohol does not play an independent role in lung cancer etiology.

Background: Currently, the acquisition of tissue from metastatic deposits is not recommended as a routine practice. Our aim was to evaluate the discordance rate of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) receptor status between primary tumor and liver metastases and its potential impact on treatment choice., Patients and Methods: We retrospectively analyzed a database including 1250 ultrasound-guided liver biopsies carried out at the European Institute of Oncology from August 1999 to March 2009. ER, PgR, and HER2 status were determined by immunohistochemistry and/or FISH. Differences between proportions were evaluated using Fisher's exact test., Results: We identified 255 consecutive patients with matched primary and liver tissue samples. Changes in ER status were observed in 37 of 255 patients (14.5%). Changes in PgR status were observed in 124 of 255 patients (48.6%). Changes in HER2 status were observed in 24 of 172 assessable patients (13.9%). We observed a discordance in receptor status (ER, PgR, and HER2) between primary tumor and liver metastases, which led to change in therapy for 31 of 255 of patients (12.1%)., Conclusions: Biopsy of metastases for reassessment of biological features should be considered in all patients, when safe and easy to carry out, since it is likely to impact treatment choice.

Background: The International Agency for Research on Cancer (IARC) concluded that alcohol consumption is related to colorectal cancer (CRC). However, several issues remain unresolved, including quantification of the association for light (≤1 drink/day) and moderate (2-3 drinks/day) alcohol drinking, investigation of the dose-response relationship, and potential heterogeneity of effects by sex, colorectal site, and geographical region., Methods: Twenty-seven cohort and 34 case-control studies presenting results for at least three categories of alcohol intake were identified from a PubMed search of articles published before May 2010. The summary relative risks (RRs) were estimated by the random effects model. Second-order fractional polynomials and random effects meta-regression models were used for modeling the dose-risk relation., Results: The RRs were 1.21 [95% confidence interval (CI) 1.13-1.28] for moderate and 1.52 (95% CI 1.27-1.81) for heavy (≥4 drinks/day) alcohol drinking. The RR for moderate drinkers, compared with non-/occasional drinkers, was stronger for men (RR = 1.24, 95% CI 1.13-1.37) than for women (RR = 1.08, 95% CI 1.03-1.13; P(heterogeneity) = 0.02). For heavy drinkers, the association was stronger in Asian studies (RR = 1.81, 95% CI 1.33-2.46; P(heterogeneity) = 0.04). The dose-risk analysis estimated RRs of 1.07 (95% CI 1.04-1.10), 1.38 (95% CI 1.28-1.50), and 1.82 (95% CI 1.41-2.35) for 10, 50, and 100 g/day of alcohol, respectively., Conclusions: This meta-analysis provides strong evidence for an association between alcohol drinking of >1 drink/day and colorectal cancer risk.

Background: cancer-testis (CT) antigens, frequently expressed in human germline cells but not in somatic tissues, may become aberrantly reexpressed in different cancer types. The aim of this study was to investigate the expression of CT antigens in breast cancer., Patients and Methods: a total of 100 selected invasive breast cancers, including 50 estrogen receptor (ER) positive/HER2 negative and 50 triple negative (TN), were examined for NY-ESO-1 and MAGE-A expression by immunohistochemistry., Results: a significantly higher expression of MAGE-A and NY-ESO-1 was detected in TN breast cancers compared with ER-positive tumors (P = 0.04). MAGE-A expression was detected in 13 (26%) TN cancers compared with 5 (10%) ER-positive tumors (P = 0.07). NY-ESO-1 expression was confirmed in nine (18%) TN tumor samples compared with two (4%) ER-positive tumors., Conclusions: MAGE-A and NY-ESO-1 CT antigens are expressed in a substantial proportion of TN breast cancers. Because of the limited therapeutic options for this group of patients, CT antigen-based vaccines might prove to be useful for patients with this phenotype of breast cancer.

Background: Tamoxifen's cost-benefit ratio for breast ductal intraepithelial neoplasia (DIN) is unclear. Since low-dose tamoxifen showed a favorable modulation of breast cancer biomarkers in phase II trials, a monoinstitutional cohort of women with DIN treated with low-dose tamoxifen or no systemic treatment was analyzed., Patients and Methods: A total of 309 patients with DIN received low-dose tamoxifen as part of institutional guidelines and were compared with 371 patients with DIN who received no systemic treatment after surgery., Results: Women with estrogen receptor (ER)/progesterone receptor (PgR) >50% DIN who were not treated had a higher incidence of breast events than women on tamoxifen [hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.00-3.12] or women with ER/PgR <50% DIN (HR 1.72; 95% CI 1.14-2.58). Among untreated patients with ER >50% DIN, recurrence was higher in PgR > or =50% DIN than in PgR <50% DIN, whereas it was similar among low PgR (<50%) DIN against which tamoxifen had no effect. No difference in endometrial cancer incidence was noted., Conclusions: High ER and especially high PgR expression is a significant adverse prognostic indicator of DIN, and low-dose tamoxifen appears to be an active treatment. Women with low-expression ER or PgR DIN do not seem to benefit from tamoxifen. A definitive clinical trial is warranted.

Background: A minority of patients treated conservatively for breast cancer will develop local or regional recurrences. Our aim was to determine how their occurrence may be linked to the evolution of the disease., Patients and Methods: We analyzed 2784 women treated for early-stage breast cancer by quadrantectomy and whole-breast irradiation in a single institution. We evaluated the prognostic factors associated with local, regional and distant recurrences and the prognostic value of local and regional recurrences on systemic progression., Results: After a median follow-up of 72 months, we observed 33 local events, 35 regional events and 222 metastases or deaths as first events (5-year cumulative incidence 1.1%, 1.2% and 7.6%, respectively). Size, estrogen receptor status, Her2/Neu and Ki-67 were associated with all three types of events, while axillary status and vascular invasion were associated only with the occurrence of metastases or death. Young age increased the risk of local recurrence. Local and regional recurrences were associated with an increased risk of systemic progression: hazard ratios 2.5 [95% confidence interval (CI) 1.1-5.8] and 5.3 (95% CI 3.0-9.5), respectively., Conclusions: Local and regional recurrences after breast-conserving surgery are rare events. They are markers of tumor aggressiveness and indicators of an increased likelihood of distant metastases.

Background: We aimed to predict disease-free survival (DFS) in patients who failed to achieve a pathologic complete remission (pCR) after preoperative chemotherapy (PC)., Patients and Methods: Data from 577 patients treated with PC and operated at the European Institute of Oncology (EIO) were used to develop a nomogram using Cox proportional hazards regression model based on both categorical (pT, positive nodes, human epidermal growth factor receptor 2 (HER2) status, vascular invasion) and continuous histological variables (estrogen receptors and Ki-67 expression) at surgery. The nomogram was tested on a second patient cohort (343 patients) treated in other institutions and subsequently operated at the EIO., Results: The nomogram for DFS based on both categorical and continuous variables had good discrimination in the training and the validation sets (concordance indices 0.73, 0.67)., Conclusion: The use of a nomogram based on the degree of selected histopathological variables can predict DFS and might help in the adjuvant therapeutic algorithm design.

Background: Better therapeutic approaches for patients with Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHL) resulted in high cure rates, at cost of serious late side effects. Second primary tumours are a major concern for long-term survivors, and breast cancer (BC) is the most common solid tumour among women treated for HD., Materials and Methods: Fifty-three women treated for primary BC with previous history of malignant lymphoma were identified in our institution, 35 with HD (66%), 18 (34%) with NHL. A comparison group was randomly selected from our database matching for each patient with previous lymphoma, two patients with primary BC (rate 1 : 2) for age, stage (pathological tumour size [pT] status and nodal status), year of diagnosis, and estrogen and progesterone status (positive versus negative). The primary end points were disease-free survival (DFS) and overall survival (OS)., Results: The two groups of patients were compared for biological features: histopathological diagnosis, grading, lymphatic invasion, c-erbB2 overexpression, and Ki-67. Considering these variables, no significant differences were observed between the two groups with the exception of Ki-67, which was found higher in those with previous HD or NHL (65% versus 49%, respectively, P = 0.0526, borderline significant). Comparing the two groups for treatment approach, no differences were found for surgical and medical therapy (endocrine therapy and chemotherapy). However, regarding patients with node-positive disease (14 versus 35 patients), five patients in the lymphoma group (36%), compared with 24 (69%) in the matched group received anthracycline-based therapy (P = 0.0345). As expected, radiotherapy was used very differently in the two groups, with 36% of patients in the study group undergoing intraoperative radiotherapy with electrons versus 10% in the control group (P = 0.0001). Five-year DFS was 54.5% for the study cohort compared with 91% for controls (P < 0.0001). Five-year OS percentages were also statistically different (86.6% and 98.6%, respectively, P = 0.031)., Conclusions: Previous history of malignant lymphoma is a negative prognostic factor for women diagnosed subsequently with BC. Some undertreatment of women with the latter might be hypothesised as the reason for the worse outcome. Influence of other variables, like previous exposure to cytotoxics, or some unknown biological features related to the previous disease and treatment, should still be investigated in the attempt to improve the dire outcome of these patients.