Controversies in treatment selection for patients with equivocal ER and HER2 results

Viale, Giuseppe

doi:10.1016/j.breast.2017.06.030

Cited by 1 publication

(2 citation statements)

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“…We found that the cyclin D1 protein as assessed by IHC was overexpressed in slightly more than half of patients with advanced breast cancer (54.3%) and the CCND1 gene was amplified in slightly more than a quarter (28.0%), as assessed by FISH. Both are compatible with recent evidence from the literature reporting cyclin D1 IHC expression ranging between 44% and 52%, and CCND1 gene amplification in 9%–30% 23–28. Of note, patients with hormone receptor-positive disease presented with higher cyclin D1 mRNA expression and CCND1 gene amplification compared with those with negative ER/PgR tumours, which was expected given the strong association between the cyclin D1 molecular pathway and the ER/PgR-mediated pathways reported consistently in the literature and confirmed in a recently reported study 27.…”

Section: Discussionsupporting

confidence: 92%

“…As expected, patients deemed to be HER2-negative and treated with trastuzumab had significantly worse clinical outcomes (PFS and overall survival) compared with patients deemed to be HER2-positive and treated with trastuzumab, exemplifying the need for an individualised therapeutic approach based on robust molecular testing, in order to avoid unnecessary and expensive treatments and to optimise clinical outcomes. To add on the above observation, the recently reported NSABP-B47 trial clearly showed that, even in patients with early-stage breast cancer with low levels of HER2, defined as IHC 1-positive or IHC 2-positive and/or in situ hybridisation-negative, adding trastuzumab to standard adjuvant chemotherapy did not improve invasive disease-free survival 28…”

Section: Discussionmentioning

confidence: 99%

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Cyclin D1 differential activation and its prognostic impact in patients with advanced breast cancer treated with trastuzumab

et al. 2019

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IntroductionWe sought to determine the level of activation of the critical components of the cyclin D1-mediated pathway and to evaluate their prognostic significance across the different molecular subtypes of advanced breast cancer.Patients and methodsThe study population comprised 219 female patients with advanced breast cancer who had been found to have human epidermal growth factor receptor 2 (HER2)-positive disease by local testing and were all treated with trastuzumab-based regimens. For all tumours, central testing for HER2 was performed, and cyclin D1 gene (CCND1) amplification, mRNA and protein expression were assessed by FISH, quantitative real-time-PCR and immunohistochemistry, respectively. Prognostic impact on clinical endpoints was evaluated with Cox regression analyses.ResultsAfter central testing, only 134 (61.2%) of 219 patients were confirmed to have HER2 gene amplification by FISH and/or 3+ HER2 protein expression by immunohistochemistry. After a median follow-up time of 136.0 months (95% CI 123.3 to 148.9), 105 (78.4%) HER2-positive patients and 76 (89.4%) HER2-negative patients had died, while 80% of the former and 87.1% of the latter had experienced a disease relapse. Patients with positive oestrogen receptor/progesterone receptor status presented with higher cyclin D1 mRNA expression. In the HER2-negative subgroup, patients with negative cyclin D1 protein expression were at higher risk of progression (HR= 1.66, 95%CI 1.01 to 2.72, Wald’s p=0.045). Among de novo metastatic patients, the risk of progression was higher for patients with non-amplified CCND1 tumours (HR= 2.00, 95% CI 1.03 to 3.90, p=0.041).ConclusionAberrant activation of the cyclin D1-mediated pathway appears to reduce the risk of progression in HER2-negative tumours, but not in HER2-positive ones.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%