Distinct HR expression patterns significantly affect the clinical behavior of metastatic HER2+ breast cancer and degree of benefit from novel anti-HER2 agents in the real world setting

We analyzed data from 738 HER2\u2010positive metastatic breast cancer (mbc) patients treated with pertuzumab\u2010based regimens and/or T\u2010DM1 at 45 Italian centers. Outcomes were explored in relation to tumor subtype assessed by immunohistochemistry (IHC). The median progression free survival at first\u2010line (mPFS1) was 12 months. Pertuzumab as first\u2010line conferred longer mPFS1 compared to other first\u2010line treatments (16 vs 9 months, p=0.0001), regardless of IHC subtype. Median PFS in second\u2010line (mPFS2) was 7 months, with no difference by IHC subtype, but it was more favorable with T\u2010DM1 compared to other agents (7 vs 6 months, p=0.03). There was no PFS2 gain in patients with tumors expressing both hormonal receptors (HRs) (p=0.17), while a trend emerged for tumors with one HR (p=0.05). Conversely, PFS2 gain was significant in HRs\u2010negative tumors (p=0.04). Median overall survival (mOS) was 74 months, with no significant differences by IHC subtypes. Survival rates at 2 and 3 years in patients treated with T\u2010DM1 in second\u2010line following pertuzumab were significantly lower compared to pertuzumab\u2010na\uefve patients(p=0.01). When analyzed by IHC subtype, the outcome was confirmed if both HRs or no HRs were expressed (p=0.02 and p=0.006, respectively). Our results confirm that HRs expression impacts the clinical behavior and novel treatment\u2010related outcomes of HER2\u2010positive tumors when treatment sequences are considered. Moreover, multivariate analysis showed that HRs expression had no effect on PFS and OS. Further studies are warranted to confirm our findings and clarify the interplay between HER2 and estrogen receptor (ER) pathways in HER2\u2010positive (mbc) patients

\u201cTriple positive\u201d early breast cancer: an observational multicenter retrospective analysis of outcome

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 6450% 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

A retrospective multicentric observational study of trastuzumab emtansine in HER2 positive metastatic breast cancer: a real- world experience

We addressed trastuzumab emtansine (T-DM1) e cacy 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 signi cant 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 bene t 60.9%. Median progression-free and median overall survival were 6 and 20 months, respectively. Overall, no di erences 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 bene t (p<0.0001), while overall survival was positively a ected by lower ECOG PS (p<0.0001), absence of brain metastases (p 0.05), and clinical bene t (p<0.0001). Our results are comparable with those from randomized trials. Further studies are warranted to con rm and interpret our data on apparently lower T-DM1 e cacy when given as second-line treatment after pertuzumab, and on the optimal sequence order

Palbociclib plus endocrine therapy in HER2 negative, hormonal receptor-positive, advanced breast cancer: A real-world experience

Data from 423 human epidermal growth factor receptor 2-negative (HER2-), hormone receptor-positive (HR+) advanced breast cancer (aBC) patients treated with palbociclib and endocrine therapy (ET) were provided by 35 Italian cancer centers and analyzed for treatment outcomes. Overall, 158 patients were treated in first line and 265 in second/later lines. We observed 19 complete responses and 112 partial responses. The overall response rate (ORR) was 31% (95% confidence interval [CI], 26.6-35.4) and clinical benefit was 52.7% (95% CI, 48-57.5). ORR was negatively affected by prior exposure to everolimus/exemestane (p = 0.002) and favorably influenced by early line-treatment (p &lt; 0.0001). At 6 months, median progression-free survival was 12 months (95% CI, 8-16) and median overall survival was 24 months (95% CI, 17-30). More favorable outcomes were associated with palbociclib in early lines, no visceral metastases and no prior everolimus/exemestane. The main toxicity reported was neutropenia. Our results provide further support to the use of palbociclib with ET in HER2-, HR+ aBC. Differences in outcomes across patients subsets remain largely unexplained