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

Alves, Fatima Regina Abreu; Gil, Lúcia; Matos, Leonor Vasconcelos de; Baleiras, Ana; Vasques, Carolina; Neves, Maria Teresa; Ferreira, A.; Fontes‐Sousa, Mário; Miranda, Helena; Martins, Ana

doi:10.7759/cureus.22330

Cited by 16 publications

(22 citation statements)

References 24 publications

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“…We reported a significant association between HER2-low and reduced pCR overall. This finding was consistent with the pooled analysis of data from clinical trial ( Denkert et al, 2021 ) and in contrast with results from retrospective studies involving few patients and showing no impact of HER2 status on response to therapy ( de Moura Leite et al, 2021 ; Alves et al, 2022 ; Domergue et al, 2022 ). The predictive value of HER2-low appeared to be more pronounced in HR-positive than -negative cases, though the difference did not reach the statistical significance.…”

Section: Discussionsupporting

confidence: 89%

Moving HER2-low breast cancer predictive and prognostic data from clinical trials into the real world

Cosimo

Rocca

Ljevar

et al. 2022

Front. Mol. Biosci.

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Background: Previous data, mostly from clinical trials, reported that HER2-low status is associated with low pathological complete response (pCR), and favourable prognosis. Since these findings suggest the existence of an additional breast cancer subtype, we questioned if the predictive/prognostic value of HER2-low was also relevant in the real world.Methods: Data from non-metastatic breast cancer patients treated with neoadjuvant chemotherapy and surgery (2009–2020) were retrieved from our institutional prospectively-maintained registry. Univariable and multivariable logistic models were implemented to study the association between pCR and baseline HER2 status. Univariable analysis of disease-free survival (DFS) was performed through Kaplan-Meier survival curves and log-rank tests.Results: Starting from a total of 790 consecutive cases, we identified 444 newly-diagnosed breast cancer patients featuring HER2 immunohistochemistry (IHC) 0 (HER2-0, n = 109), and 1 + or IHC 2+/in situ hybridization negative (HER2-low, n = 335) receiving anthracycline and taxane-based regimens in 88.9% of cases. Most of the patients were diagnosed with stage II (67.3%) and there was no difference of disease presentation according to HER2-status. pCR was attained by 71 (16.0%) patients and was significantly associated with increased DFS (p = 0.031). Compared to HER2-0, HER2-low cases were more likely hormone receptor-positive (81.2% vs. 43.1%, p < 0.001), well-differentiated (47.5% vs. 26.6%, p = 0.001), less proliferative (21.5% vs. 8.3%, p = 0.001) and less responsive to treatment (pCR 11.6% vs. 29.4%, p < 0.0001). There was no difference in DFS according to HER2 status, though hormone-receptor (HR) negative/HER2-low cases tended to have a worse prognosis compared to HR-negative/HER2-0. By pCR achievement, 3-years DFS was 87.5.% (75.1–100%) vs. 71.6% (65.9–77.8%) (p = 0.161) in HER2-low and 89.1% (75.8–100%) vs. 72.1% (59.7–87.0%) (p = 0.092) in HER2-0.Conclusion: Our real-world data show that HER2-low breast cancer patients represent roughly a half of the cases treated with neoadjuvant therapy, and have poor treatment response. In absence of pCR, HER2-low breast cancer patients have a dismal prognosis, especially when primary tumor hormone receptor status is negative. Studies are therefore needed to define the biology of these tumors for new therapeutic targets and to incorporate HER2-targeting agents in early-stage treatment.

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Section: Discussionsupporting

confidence: 89%

Moving HER2-low breast cancer predictive and prognostic data from clinical trials into the real world

Cosimo

Rocca

Ljevar

et al. 2022

Front. Mol. Biosci.

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“…We evaluated 15 studies 4,10,12–14,16,18,19,22,24,25–28 ; 7 new studies 10,13,14,16,19,24,27 were included and 6 studies 3,15,20,23,29,30 were excluded from evaluation of the OS of the overall population.…”

Section: Resultsmentioning

confidence: 99%

“…In all, 14 studies 3,4,12,15,18,20,22,23,25,26,[28][29][30]32 (n = 81,486) were included to evaluate the OS of the overall population. The results demonstrated that patients with HER2-low BC had better OS than those with HER2-zero BC (HR = 0.90; 95% CI: 0.85-0.97; p = 0.003), despite considerable heterogeneity between the studies (p < 0.01; I 2 = 93%) (Figure 2(a); Table 2).…”

Section: Comparison Of Os Between Patients With Her2-low and Her2-zer...mentioning

confidence: 99%

The association between HER2-low expression and prognosis of breast cancer: a systematic review and meta-analysis

et al. 2023

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Background: The use of antibody–drug conjugates for the treatment of advanced-stage human epidermal growth factor receptor 2 (HER2)-low expression in breast cancer (BC) has shown prominent curative effects, which has led to increased academic interest. However, the role of HER2-low expression in the prognosis of BC remains controversial. Methods: We conducted a systematic search of the PubMed, Embase, and Cochrane library databases and several oncology conferences until 20 September 2022. We used fixed- and random-effects models to calculate odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) for overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and pathological complete response (pCR) rates. Results: Overall, 26 studies encompassing 677,248 patients were included in the meta-analysis. Patients with HER2-low BC showed significantly better OS than those with HER2-zero BC in the overall population (HR = 0.90; 95% CI: 0.85–0.97) and hormone receptor-positive population (HR = 0.98; 95% CI: 0.96–0.99), whereas no significant difference was observed in the OS of the hormone receptor-negative population ( p > 0.05). In addition, there was no significant difference in the DFS of the overall and hormone receptor-negative population ( p > 0.05), but better DFS than those with HER2-zero BC in the hormone receptor-negative population (HR = 0.96; 95% CI: 0.94–0.99). There was also no significant difference in the PFS of the overall population, hormone receptor-positive, and hormone receptor-negative population ( p > 0.05). Patients with HER2-low BC had a lower pCR rate after neoadjuvant treatment than those with HER2-zero BC. Conclusions: Compared to patients with HER2-zero BC, those with HER2-low BC had better OS in the overall population and hormone receptor-positive population, DFS in hormone receptor-positive population and lower pCR in the overall population. The biological differences between HER2-low and HER2-zero BCs, particularly in hormone receptor-positive patients, and the relationship between HER2-low expression status and prognosis need to be explored further.

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“…However, some studies have shown no statistical difference in HER2-low tumor pCR compared to HER2-0 tumors. The study by Alves, F. R. concluded [31] that the subgroup with low HER2 achieved a lower pCR rate, but this difference was not statistically signi cant. de Moura Leite, L.'s study [37] reported no difference in the pCR rate between the two groups either.…”

Section: Discussionmentioning

confidence: 96%

“…A retrospective examination of 281 cases revealed that HER2-low breast cancers had considerably lower Ki-67 and higher ER-positive than HER2-0 breast cancers [30]. The study by Alves, F. R. showed [31] that these two subgroups differed signi cantly in hormone receptor status and proliferation grade (Ki67), with statistically signi cant differences in hormone and progesterone receptors. The Korean Breast Cancer Association conducted a nationwide investigation revealed that breast cancer with low HER2 was signi cantly associated with a lower Ki-67 marker index [18].…”

Section: Discussionmentioning

confidence: 99%

How is the clinical value of HER2-low expression in early breast cancer with the neoadjuvant setting: an ambidirectional cohort study.

Song

et al. 2023

Preprint

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Background: Cumulative studies supported that HER2 low is a biological subtype of breast cancer however controversial conclusions were made in different real-world studies. We explored the differences in clinical characteristics and short-term and long-term prognosis outcomes between HER2 0 and HER2 low early breast cancer patients using an ambidirectional cohort in China. Methods: Among 711 patients who first diagnosed with breast cancer between January 1, 2016 to December 31, 2020, those with neoadjuvant chemotherapy were screened. Finally, 303 patients were included in our analysis and 90 patients (29.7%) with HER2 = 0 and 213 patients (70.3%) with HER2 = 1+. Propensity score method with inverse probability of treatment weighting was applied to account for the confounders. Results from weighted Kaplan-Meier curve and log-rank test, weighted logistic and cox regression were used to compare two groups. Results: Regarding the baseline and clinical characteristics between HER2-low and HER2-0 group. Family history of caner, ER, PR, HR, Ki-67 labeling index and treatment regimens were observed different. 35% patients used EC-T/EC-P/AC-P treatment. Regarding the bpCR, ORR and rwOS, after multivariate adjustment and propensity score method, no evidence indicated any differences between two groups. Conclusions: HER2-low as a specific biological subtype remains difficult. The HER2-low expression can differ from the therapeutic value in neoadjuvant setting among early breast cancer patients. Further research on the understanding of HER2 low breast cancer is necessary.

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

Cited by 16 publications

References 24 publications

Moving HER2-low breast cancer predictive and prognostic data from clinical trials into the real world

Moving HER2-low breast cancer predictive and prognostic data from clinical trials into the real world

The association between HER2-low expression and prognosis of breast cancer: a systematic review and meta-analysis

How is the clinical value of HER2-low expression in early breast cancer with the neoadjuvant setting: an ambidirectional cohort study.

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