Targeted Approaches to HER2-Low Breast Cancer: Current Practice and Future Directions

Lai, Heng-Zhou; Han, Jie-Rong; Xi, Fu; Ren, Yi-Feng; Li, Zhuohong; You, Feng-Ming

doi:10.3390/cancers14153774

Cited by 14 publications

(8 citation statements)

References 164 publications

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“…To characterize this cohort with stage I TNBC tumors, we evaluated patient DFS, OS, and background (age, tumor size, NG, HER2/ER/PgR status, surgical procedure, and whether adjuvant radiotherapy or chemotherapy was administered). Among these breast cancer-related factors, HER2 1+, 2+, and ISH negative were termed HER2-low, which has been reported to have different characteristics from the HER2-0 group ( 18 ). Therefore, we focused on HER2-low, which is present in some TNBC cases, as a breast cancer-related factor affecting recurrence risk and treatment choice for patients with TNBC.…”

Section: Discussionmentioning

confidence: 99%

Low HER2 expression is a predictor of poor prognosis in stage I triple-negative breast cancer

et al. 2023

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IntroductionTriple-negative breast cancer (TNBC) is negative for hormone receptors and human epidermal growth factor receptor 2 (HER2). In stage I TNBC, adjuvant therapy or follow-up are performed according to risk factors, but clinical trial data is scarce. In recent years, it has been reported that HER2-low cases (1+/2+ and in situ hybridization negative) have different prognoses than HER2-0 cases. However, the risk of recurrence and risk factors in this HER2-low population for stage I TNBC have not yet been investigated.MethodsHerein, out of 174 patients with TNBC who underwent surgery from June 2004 to December 2009 at the National Cancer Center Hospital (Tokyo), we retrospectively examined 42 cases diagnosed as T1N0M0 TNBC after excluding those treated with preoperative chemotherapy.ResultsAll patients were female, the median age was 60.5 years, and 11 cases were HER2-low and 31 cases were HER2-0. The median follow-up period was 121 months. Postoperative adjuvant therapy was administered in 30 patients and recurrence occurred in 8 patients. HER2-low cases showed a significantly shorter disease-free survival (HR: 7.0; 95% CI: 1.2– 40.2; P=0.0016) and a trend towards shorter overall survival (hazard ratio [HR]: 4.2, 95% confidence interval [CI]: 0.58–31.4) compared with that of HER2-0 cases. HER2 was also identified as a factor for poor prognosis from the point- estimated values in univariate and multivariate analyses after confirming that there was no correlation between the other factors.ConclusionFor patients with stage I TNBC, the HER2-low population had a significantly worse prognosis than the HER2-0 population.

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Section: Discussionmentioning

confidence: 99%

Low HER2 expression is a predictor of poor prognosis in stage I triple-negative breast cancer

et al. 2023

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“…Initial HER2-targeted agents were ineffective against HER2low breast cancer (36). However, the ADC trastuzumab deruxtecan recently demonstrated efficacy in this setting (37).…”

Section: Breast Cancermentioning

confidence: 99%

Targeted thorium-227 conjugates as treatment options in oncology

et al. 2023

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Targeted alpha therapy (TAT) is a promising approach for addressing unmet needs in oncology. Inherent properties make α-emitting radionuclides well suited to cancer therapy, including high linear energy transfer (LET), penetration range of 2–10 cell layers, induction of complex double-stranded DNA breaks, and immune-stimulatory effects. Several alpha radionuclides, including radium-223 (223Ra), actinium-225 (225Ac), and thorium-227 (227Th), have been investigated. Conjugation of tumor targeting modalities, such as antibodies and small molecules, with a chelator moiety and subsequent radiolabeling with α-emitters enables specific delivery of cytotoxic payloads to different tumor types. 223Ra dichloride, approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) with bone-metastatic disease and no visceral metastasis, is the only approved and commercialized alpha therapy. However, 223Ra dichloride cannot currently be complexed to targeting moieties. In contrast to 223Ra, 227Th may be readily chelated, which allows radiolabeling of tumor targeting moieties to produce targeted thorium conjugates (TTCs), facilitating delivery to a broad range of tumors. TTCs have shown promise in pre-clinical studies across a range of tumor-cell expressing antigens. A clinical study in hematological malignancy targeting CD22 has demonstrated early signs of activity. Furthermore, pre-clinical studies show additive or synergistic effects when TTCs are combined with established anti-cancer therapies, for example androgen receptor inhibitors (ARI), DNA damage response inhibitors such as poly (ADP)-ribose polymerase inhibitors or ataxia telangiectasia and Rad3-related kinase inhibitors, as well as immune checkpoint inhibitors.

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“…Scholars have found that they can play a role in BC patients with HER2-low. 59,62,63 In addition, tri-specific antibodies are also gradually on the stage. Zheng et al 64 found that trispecific antibodies consisting of HER2, CD3, and CD28 arms can promote the regression of tumors with HER2 overexpression or low expression by stimulating CD4 T cells at a very low dose, which may provide the new drug development for the treatment of HER2-low/ zero BC.…”

Section: Treatment Of Targeting Her2 Receptorsmentioning

confidence: 99%

“…Zenocutuzumab is antibody‐dependent cell‐mediated cytotoxicity (ADCC)‐enhanced IgG antibody that targets HER2 and Her3 and blocks neuregulin signaling by preventing the formation of heterodimers. Scholars have found that they can play a role in BC patients with HER2‐low 59,62,63 . In addition, tri‐specific antibodies are also gradually on the stage.…”

Section: Treatment Of Her2‐low/zero Breast Cancermentioning

confidence: 99%

The trichotomy of HER2 expression confers new insights into the understanding and managing for breast cancer stratified by HER2 status

Jiang

Liu

et al. 2023

Intl Journal of Cancer

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Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor that plays a carcinogenic role in breast cancer (BC) through gene amplification, mutation, or overexpression. Traditional methods of HER2 detection were divided into positive (immunohistochemistry (IHC) 3+/fluorescence in situ hybridization (FISH) amplification) and negative (IHC 2+/FISH−, IHC 1+, IHC 0) according to the dichotomy method. Anti‐HER2‐targeted therapies, such as trastuzumab and pertuzumab, have significantly improved the prognosis of HER2‐positive patients. However, up to 75% to 85% of patients remain HER2‐negative. In recent years, with the rapid development of molecular biology, gene detection technology, targeted therapy, and immunotherapy, researchers have actively explored the clinicopathological characteristics, molecular biological characteristics, treatment methods, and HER2 detection methods of HER2‐low/zero breast cancer. With the clinical efficacy of new anti‐HER2 targeted drugs, accurate classification of breast cancer is very important for the treatment choice. Therefore, the following review summarizes the necessity of developing HER2 detection methods, and the clinicopathological and drug treatment characteristics of patients with HER2‐low/zero, to light the dawn of the treatment of breast cancer patients with HER2‐low/zero expression.

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Targeted Approaches to HER2-Low Breast Cancer: Current Practice and Future Directions

Cited by 14 publications

References 164 publications

Low HER2 expression is a predictor of poor prognosis in stage I triple-negative breast cancer

Low HER2 expression is a predictor of poor prognosis in stage I triple-negative breast cancer

Targeted thorium-227 conjugates as treatment options in oncology

The trichotomy of HER2 expression confers new insights into the understanding and managing for breast cancer stratified by HER2 status

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