We addressed trastuzumab emtansine (T-DM1) efficacy in HER2+ metastatic breast cancer patients treated in real-world practice, and its activity in pertuzumab-pretreated patients. We conducted a retrospective, observational study involving 23 cancer centres, and 250 patients. Survival data were analyzed by Kaplan Meier curves and log rank test. Factors testing significant in univariate analysis were tested in multivariate models. Median follow-up was 15 months and median T-DM1 treatment-length 4 months. Response rate was 41.6%, clinical benefit 60.9%. Median progression-free and median overall survival were 6 and 20 months, respectively. Overall, no differences emerged by pertuzumab pretreatment, with median progression-free and median overall survival of 4 and 17 months in pertuzumab-pretreated (p=0.13), and 6 and 22 months in pertuzumab-naïve patients (p=0.27). Patients who received second-line T-DM1 had median progression-free and median overall survival of 3 and 12 months (p=0.0001) if pertuzumab-pretreated, and 8 and 26 months if pertuzumab-naïve (p=0.06). In contrast, in third-line and beyond, median progression-free and median overall survival were 16 and 18 months in pertuzumab-pretreated (p=0.05) and 6 and 17 months in pertuzumab-naïve patients (p=0.30). In multivariate analysis, lower ECOG performance status was associated with progression-free survival benefit (p<0.0001), while overall survival was positively affected by lower ECOG PS (p<0.0001), absence of brain metastases (p 0.05), and clinical benefit (p<0.0001). Our results are comparable with those from randomized trials. Further studies are warranted to confirm and interpret our data on apparently lower T-DM1 efficacy when given as second-line treatment after pertuzumab, and on the optimal sequence order.

Background: Eribulin was recently approved in patients progressing after being treated with anthracyclines and taxanes and after two or more chemotherapy lines for advanced disease.Objectives: This multicenter observational retrospective study was performed in order to evaluate activity and tolerability of eribulin in real-world patient population.Methods: 133 advanced breast cancer patients pretreated with ≥ 2 chemotherapy lines for metastatic disease were retrospectively enrolled in the observational trial in 11 italian cancer centres.Results: A median of 5 cycles of eribulin (range, 1-15) were administered. Twenty-eight partial responses were observed, for an overall response rate of 21.1% (95%CI,14.1-28.0). A stable disease was recorded in 57 patients (42.8%), and a clinical benefit (response or stable disease lasting ≥ six months) was observed in 51 patients (38.3%, 95%CI, 30.1-46.6). The subgroup analysis showed that a significant improvement in term of partial response and clinical benefit was achieved when eribulin was administered in HER-2 negative tumors (p=0.01 and p=0.004, respectively) and when it is given as third-line (p=0.09 and p=0.02, respectively). Toxicity was manageable; fatigue is the most common side effect observed, usually of low-grade, and clearly cumulative-dose related.Conclusions: In this retrospective, observational analysis eribulin confirmed its efficacy and manageable tolerability even in real-world population and in heavily pretreated patients.

Addition of trastuzumab to adjuvant chemotherapy has dramatically reduced the risk of recurrence and has become the standard of care for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer patients. Since most data on trastuzumab benefits come from clinical trials, conducted in selected patient populations, we performed a retrospective analysis of HER2-positive early breast cancer patients treated in the “pre-trastuzumab” and “trastuzumab” eras, with the aim to determine patients' outcomes in real-world practice. 925 consecutive HER2-positive breast cancer patients treated with adjuvant chemotherapy in ten Italian oncologic centers were identified. Patients who had received adjuvant chemotherapy alone (cohort A, 352 patients), and patients who had received adjuvant chemotherapy followed or combined with trastuzumab (cohort B, 573 patients) were analyzed. Relapse rate at 3 years, relapse-free survival, and overall survival were significantly more unfavorable in the cohort A than in the cohort B (p < 0.0001). In multivariate analysis, factors related to relapse were younger age, advanced stage at diagnosis, absence of hormonal and of trastuzumab therapy. The benefit derived from the addition of trastuzumab was independent of nodal status and hormonal receptors expression. A subgroup analysis including 163 “triple positive” tumors with high levels of estrogen and progesterone receptor (TP50) suggested that addition of trastuzumab to adjuvant chemotherapy and hormonal therapy did not translate into better outcomes. In our analysis, trastuzumab benefit was confirmed in all but a small subset of TP50 tumors subgroups. In this subset further investigations are needed.

We recently found that trastuzumab benefit may be lower in a small subset of early breast cancer (BC) patients (pts) with tumors expressing high levels of both hormonal receptors (HRs), i.e. triple positive (TP). To better investigate the role of HRs in HER2 positive BC, we retrospectively identified 872 TP BC pts treated with adjuvant chemotherapy alone (cohort A-366 pts), or plus trastuzumab (cohort B-506 pts). Relapse-free-survival (RFS) and breast-cancer-specific-survival (BCSS) were evaluated. Trastuzumab improved RFS and BCSS in all the subsets analyzed, but the effect on BCSS in tumors expressing both HRs in >30% of cells (TP30), and even on RFS in tumors with both HRs expressed in >50% of cells (TP50) was not significant. Distinct patterns of relapse were observed in TP50 and no-TP50 tumors, the former showing low and constant risk in the first 5 years, a late increase beyond 5 years and modest trastuzumab effect. Trastuzumab effect tended to disappear in pts whose tumors expressed ER in >50% of cells. Multivariate analysis of RFS confirmed a significant interaction between trastuzumab and ER expression, with benefit confined to pts whose tumors expressed ER in ≤50% of cells.Our data suggest that the pattern of relapse of TP tumors with high HRs is similar to that of “luminal”, HER2 negative tumors, without clear benefit from adjuvant trastuzumab, which remains the standard treatment even in TP tumors. Confirmatory findings on the extent to which quantitative expression of HRs may impact clinical behavior of HER2 positive BC are warranted.

PurposeRecurrences and deaths are known to occur, even if less frequently, in small, node-negative breast cancer patients, and decision on adjuvant treatments remains controversial. In the present analysis, we evaluate recurrence risk in patients with pT1 a, b, c, node-negative, breast cancer, accordingly with some prognostic biological factors.MethodsWe retrospectively evaluated 900 node-negative patients (pT1a, b, c) surgery treated between 2000 and 2009 in four Italian oncologic centers. We defined 3 different cohorts: ER positive (ER+); Her-2 positive (Her-2+); and triple negative (TN).ResultspT1a was seen in 7.6% of patients, 37.7 % pT1b, 54.8 % pT1c. Concerning the 3 different cohorts, 58.2 % were ER+; 10.8 % were Her-2+; 8.2 % were TN. Overall, chemotherapy was given to 3.0 %, 27.2 %, 69.8 % of pT1a, b, c, respectively, and to 22.7 %, 58.8 %, 68.9 % of ER+, Her-2+, TN subgroups. At a median follow-up of 67 months, 5-year DFS was 96.3 %, 89.2 %, 89.4 % in pT1a, b, c, respectively (100 %, 93.6 %, 89.8 % in ER+; 100 %, 78.7 %, 85.0 % in Her-2+; 100 %, 76.8 %, 85.2 % in TN) (p = ns). At multivariate analysis, histologic grade and Ki-67 resulted independent prognostic factors. Overall, 5-year OS was 98 %, without differences among pT1a, b, c, or among the 3 cohorts.ConclusionsOverall, 5-year DFS was very favorable in this series of small, node-negative breast cancers, but Her-2+ and TN cohorts have a higher recurrence rate than ER+ cohort (p < 0.0001); pT1c, but also pT1b, in Her-2+ and TN subgroups, have a worse outcome, and effective chemotherapy treatment should be considered in these unfavorable subgroups.