Evolving concepts in HER2 evaluation in breast cancer: Heterogeneity, HER2-low carcinomas and beyond

Marchiò, Caterina; Annaratone, Laura; Marques, Ana; Casorzo, Laura; Berrino, Enrico; Sapino, Anna

doi:10.1016/j.semcancer.2020.02.016

Cited by 231 publications

(195 citation statements)

References 107 publications

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“…These novel treatment strategies should be focused on the hallmarks of cancer that differentiate tumor cells from normal ones in order to reduce the apparition of side toxicology. One of such hallmarks is the overexpression of HER2 that occurs in 15-20% of breast cancers that are diagnosed, and also in other types of solid tumors, such as gastric, ovarian, or lung carcinomas [3][4][5]91]. HER2 overexpression has been associated with more aggressive tumors and a worse prognosis for patients for a long time but, since Tmab development, it has also offered a way to upgrade treatment specificity [4].…”

Section: Discussionmentioning

confidence: 99%

“…Among the different types of cancer, breast cancer has the second highest incidence, and about 11–12% of the total of new cancer cases that were diagnosed in 2018 were from this tissue [ 2 ]. Although there are manifold phenotypes of this disease, approximately 15–20% of breast cancer cases present an overexpression of the human epidermal growth factor receptor-2 (HER2) [ 3 , 4 ], which in addition is also overexpressed in other types of solid tumors [ 5 ]. On one hand, the increased expression of this tyrosine kinase receptor is related to cell proliferation, migration, and invasion and, thus, to a poor prognosis for patients and a higher risk of disease recurrence [ 4 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Although there are manifold phenotypes of this disease, approximately 15–20% of breast cancer cases present an overexpression of the human epidermal growth factor receptor-2 (HER2) [ 3 , 4 ], which in addition is also overexpressed in other types of solid tumors [ 5 ]. On one hand, the increased expression of this tyrosine kinase receptor is related to cell proliferation, migration, and invasion and, thus, to a poor prognosis for patients and a higher risk of disease recurrence [ 4 , 6 ]. Nevertheless, on the other hand, it has offered the possibility of developing guided-treatment approaches [ 4 ], solving one major drawback of conventional chemotherapy: its lack of specificity.…”

Section: Introductionmentioning

confidence: 99%

“…On one hand, the increased expression of this tyrosine kinase receptor is related to cell proliferation, migration, and invasion and, thus, to a poor prognosis for patients and a higher risk of disease recurrence [ 4 , 6 ]. Nevertheless, on the other hand, it has offered the possibility of developing guided-treatment approaches [ 4 ], solving one major drawback of conventional chemotherapy: its lack of specificity.…”

Section: Introductionmentioning

confidence: 99%

“…[83],2 [89],3 [99],4 [100],5 [104],6 [105]. AF-HPA: auristatin F-hydroxypropylamide; NSCLC: non-small cell lung carcinoma; PBD-MA: pyrrolo[2,1-c][1,4]benzodiazepine monoamide.…”

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confidence: 99%

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Trastuzumab: More than a Guide in HER2-Positive Cancer Nanomedicine

2020

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HER2 overexpression, which occurs in a fifth of diagnosed breast cancers as well as in other types of solid tumors, has been traditionally linked to greater aggressiveness. Nevertheless, the clinical introduction of trastuzumab has helped to improve HER2-positive patients’ outcomes. As a consequence, nanotechnology has taken advantage of the beneficial effects of the administration of this antibody and has employed it to develop HER2-targeting nanomedicines with promising therapeutic activity and limited toxicity. In this review, the molecular pathways that could be responsible for trastuzumab antitumor activity will be briefly summarized. In addition, since the conjugation strategies that are followed to develop targeting nanomedicines are essential to maintaining their efficacy and tolerability, the ones most employed to decorate drug-loaded nanoparticles and liposomes with trastuzumab will be discussed here. Thus, the advantages and disadvantages of performing this trastuzumab conjugation through adsorption or covalent bindings (through carbodiimide, maleimide, and click-chemistry) will be described, and several examples of targeting nanovehicles developed following these strategies will be commented on. Moreover, conjugation methods employed to synthesized trastuzumab-based antibody drug conjugates (ADCs), among which T-DM1 is well known, will be also examined. Finally, although trastuzumab-decorated nanoparticles and liposomes and trastuzumab-based ADCs have proven to have better selectivity and efficacy than loaded drugs, trastuzumab administration is sometimes related to side toxicities and the apparition of resistances. For this reason also, this review focuses at last on the important role that newer antibodies and peptides are acquiring these days in the development of HER2-targeting nanomedicines.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…[83],2 [89],3 [99],4 [100],5 [104],6 [105]. AF-HPA: auristatin F-hydroxypropylamide; NSCLC: non-small cell lung carcinoma; PBD-MA: pyrrolo[2,1-c][1,4]benzodiazepine monoamide.…”

mentioning

confidence: 99%

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Trastuzumab: More than a Guide in HER2-Positive Cancer Nanomedicine

2020

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Comparison of Management and Outcomes in ERBB2-Low vs ERBB2-Zero Metastatic Breast Cancer in France

et al. 2022

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IMPORTANCE ERBB2-low (ie, ERBB2 immunohistochemistry score of 1+ or 2+ in the absence of ERBB2 gene amplification) breast cancer (BC) is a new entity, with emerging dedicated treatments. Little is known about its prognosis and response to conventional therapy compared with ERBB2-zero breast tumors (ie, those with an immunohistochemistry score of 0). OBJECTIVE To compare the outcomes for patients with ERBB2-low metastatic BC (MBC) with those of patients with ERBB2-zero MBC. DESIGN, SETTING, AND PARTICIPANTS This cohort study was conducted from the Epidemiological Strategy and Medical Economics MBC platform and included patients with MBC

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Clinical characteristics, tumor‐infiltrating lymphocytes, and prognosis in HER2‐low breast cancer: A comparison study with HER2‐zero and HER2‐positive disease

Tong

Fei

et al. 2023

Cancer Medicine

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IntroductionHER2‐low breast cancer is a gradually recognized and unexplored group of diseases. We aimed to investigate the clinical and prognosis features and to identify the role of stromal tumor‐infiltrating lymphocytes (sTILs) in this population.MethodsConsecutive primary breast cancer patients treated between January 2009 to June 2013 were retrospectively reviewed. HER2‐low was defined as immunohistochemistry (IHC) 1+, or 2+ and fluorescence in situ hybridization (FISH) negative. sTILs were scored following the international guidelines. Clinicopathologic features and survival were compared according to HER2 and sTILs category.ResultsA total of 973 breast cancer patients were enrolled, including 615 (63.2%) HER2‐low patients. HER2‐low patients shared more similarity with HER2‐0 cases in clinicopathological features. sTILs in HER2‐Low patients was comparable to HER2‐0 patients (p = 0.064), both significantly lower than HER2‐positive ones (p < 0.001). Meanwhile, tumors with sTILs ≥50% accounted for the least proportion of HER2‐low cases (p < 0.001). HER2 status had no significant influence on recurrence‐free survival (RFS, p = 0.901) in the whole population. However, in the estrogen receptor (ER)‐negative subgroup, HER2‐low was related to worse RFS (p = 0.009) and OS (p = 0.001) compared with HER2‐positive ones. sTILs increment was an independent favorable prognostic factor in the whole (OS, p = 0.003; RFS, p = 0.005) and HER2‐low population (OS, p = 0.007; RFS, p = 0.009) after adjusted to clinicopathological parameters.ConclusionsHER2‐low patients shared similar clinicopathological features with HER2‐0 rather than HER2‐positive cases and had relatively low sTILs. ER‐negative/HER2‐low patients had significantly inferior survival. sTILs increment was independently associated with favorable survival in the HER2‐low group, suggesting a potential benefit from a novel treatment strategy.

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Evolving concepts in HER2 evaluation in breast cancer: Heterogeneity, HER2-low carcinomas and beyond

Cited by 231 publications

References 107 publications

Trastuzumab: More than a Guide in HER2-Positive Cancer Nanomedicine

Trastuzumab: More than a Guide in HER2-Positive Cancer Nanomedicine

Comparison of Management and Outcomes in ERBB2-Low vs ERBB2-Zero Metastatic Breast Cancer in France

Clinical characteristics, tumor‐infiltrating lymphocytes, and prognosis in HER2‐low breast cancer: A comparison study with HER2‐zero and HER2‐positive disease

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