Prognostic impact of HER2-low expression in hormone receptor positive early breast cancer

Abstract

Background: Recent data suggest that human epidermal growth factor receptor 2 (HER2)-low breast cancer may represent a distinct entity. We aimed to compare disease characteristics and outcomes between HER2-low and HER2-0 in estrogen receptor (ER) positive, early-stage breast cancer. Methods: A single center retrospective study comprising all women with ER positive, HER2 negative early breast cancer, for whom an Oncotype DX test was performed between 2005 and 2012. Women were grouped to HER2-low (immunohistochemistry þ1 or þ2 and in situ hybridization not amplified) or HER2-0. Clinico-pathological features and Oncotype recurrence score (RS) were collected. Data on overall-survival (OS), disease-free survival (DFS) and distant disease-free survival (DDFS) were evaluated according to HER2 expression status. Results: 608 women were included, of which 304 women had HER2-0 and 304 had HER2-low disease. Lobular subtype was significantly more common in HER-0 compared to HER2-low disease (17% vs. 8%, p ¼ 0.005). The prevalence of other clinic-pathological characteristics and long-term prognosis were comparable between both groups. For women with high genomic risk (RS > 25), HER2-low expression was associated with significantly favorable OS (HR ¼ 0.31, 95% CI 0.11e0.78, p ¼ 0.01), DFS (HR ¼ 0.40, 95% CI 0.20e0.82, p ¼ 0.01) and DDFS (HR ¼ 0.26, 95% CI 0.11e0.63, P ¼ 0.002) compared to women with HER2-0. For women with low genomic risk (RS 25), long-term prognosis was unrelated to HER2 expression. Conclusion:The prognostic impact of HER2-low expression in early-stage luminal disease varies across the genomic risk, with significant favorable outcomes of HER2-low expression compared to HER2-0 in women with high genomic risk.

Clinical significance of HER2-low expression in early breast cancer: a nationwide study from the Korean Breast Cancer Society

“…Moreover, a trend, though not statistically significant, toward prolonged DFS and OS was observed for HER2-low breast cancer in patients with HR-positive breast cancer. Mutai et al analyzed data from 608 patients with HR-positive early breast cancer, and found that HER2-low breast cancer was associated with significant improvement in OS and DFS compared with HER-IHC 0 breast cancer in patients with high genomic risk [ 22 ]. Schettini et al analyzed overall survival data from 1,304 patients with metastatic breast cancer, and reported that there was no significant difference in OS between HER2-low and HER2-IHC 0 breast cancer in case of both HR-positive breast cancer and TNBC [ 19 ].…”

HER2 expression, copy number variation and survival outcomes in HER2-low non-metastatic breast cancer: an international multicentre cohort study and TCGA-METABRIC analysis

“…Schettini et al demonstrated that within hormone receptor-positive BCs, expression of ERBB2 and luminal-related genes was higher in HER2-low BCs compared to HER2-zero; there was no differential expression of genes in hormone receptor-negative BCs according to HER2 expression [ 15 ]. Interestingly, in early ER-positive BCs with high genomic risk (OncotypeDx risk score > 25), Mutai et al observed more favourable outcomes of HER2-low compared to HER2-zero tumours [ 36 ]. It is worth noting that in advanced BC, a modestly superior OS (HR 0.95, 95% CI 0.91 to 0.99) was also observed by Frenel et al ( n = 15,054) for HER2-low BC in a preliminary report [ 35 ], particularly for the hormone receptor-negative subgroup, although smaller studies have not detected significant differences [ 15 – 17 ].…”

Impact of Human Epidermal Growth Factor Receptor 2 (HER2) Low Status in Response to Neoadjuvant Chemotherapy in Early Breast Cancer

“…However, this is not true for other factors such as tumor grade; moreover, there was no difference between luminal HER2-low and TNBC HER2-low (p = 0.36) and thus no impact of hormonal receptor in the HER2-low group. Furthermore, despite the chemosensitivity of HER2+ disease, whether HER2-low expression is predictive of response to CT is unclear and further research is needed [ 10 ].…”

“…The HER2-low subgroup is currently not targetable with standard anti-HER2 agents as demonstrated in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B47 trial, which showed no clinical benefit by adding trastuzumab, an anti-HER2 targeted therapy, to adjuvant chemotherapy (CT) in the high-risk population [ 7 , 9 ]. However, more recent clinical data from non-randomized trials have shown a potential advantage of new anti-HER2 therapies in HER2-low pretreated patients and have yielded promising results [ 10 ]. These findings show that antibody-drug conjugates (ADC), in particular, trastuzumab deruxtecan [ 11 , 12 ] and trastuzumab duocarmazine [ 13 ], may have clinical activity in tumors that have low to moderate levels of HER2 expression beside classical HER2+ BC, revealing objective response rates ranging between 32% and 37% in the HER2-low population [ 7 , 11 - 13 ].…”