Clinicopathologic Factors Associated With Response to Neoadjuvant Anti-HER2–Directed Chemotherapy in HER2-Positive Breast Cancer

Meisel, Jane L.; Zhao, Jing; Suo, Aili; Zhang, Chao; Wei, Zhimin; Taylor, Caitlin; Aneja, Ritu; Krishnamurti, Uma; Nahta, Rita; O’Regan, Ruth; Li, Xiaoxian

doi:10.1016/j.clbc.2019.09.003

Cited by 25 publications

(23 citation statements)

References 24 publications

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“…Ki-67 index, a marker of cell proliferation, has also been found to be an independent predictor of pCR when measured by objective quantitative methods [12]. Other studies have confirmed that molecular subtype (ER and PgR expression and HER2 status) and Ki-67 index were significant independent predictors of pCR and disease-free survival [13][14][15]. Increased levels of stromal tumorinfiltrating lymphocytes (TILs) on prechemotherapy biopsy also have predicted higher rates of pCR response to NAC, particularly in HER2+ or triple-negative disease [16].…”

Section: Introductionmentioning

confidence: 94%

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HER2 Testing Characteristics Can Predict Residual Cancer Burden following Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer

Lillemoe

Rendi

Tsai

et al. 2021

International Journal of Breast Cancer

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Objectives. The response to HER2-targeted neoadjuvant chemotherapy (NAC) in HER2-positive (+) breast cancer can be quantified using residual cancer burden (RCB) pathologic evaluation to predict relapse free/overall survival. However, more information is needed to characterize the relationship between patterns of HER2 testing results and response to NAC. We evaluated clinicopathologic characteristics associated with RCB categories in HER2+ patients who underwent HER2-directed NAC. Methods. A retrospective chart review was conducted with Stage I–III HER2+ breast cancer cases following NAC and surgical resection. HER2 immunohistochemistry (IHC) staining and fluorescence in situ hybridization (FISH), histologic/clinical characteristics, hormone receptor status, and RCB scores (RCB-0, RCB-I, RCB-II, and RCB-III) were evaluated. Results. 64/151 (42.4%) patients with HER2+ disease had pathologic complete response (pCR). Tumors with suboptimal response (RCB-II and RCB-III) were more likely to demonstrate less than 100% HER2 IHC 3+ staining ( p < 0.0001 ), lower HER2 FISH copies ( p < 0.0001 ), and lower HER2/CEP17 ratios ( p = 0.0015 ) compared to RCB-I and RCB-II responses. Estrogen receptor classification using ≥10% versus ≥1% staining showed greater association with higher RCB categories. Conclusions. HER2+ characteristics show differing response to therapy despite all being categorized as positive; tumors with less than 100% IHC 3+ staining, lower HER2 FISH copies, and lower HER2/CEP17 ratios resulted in higher RCB scores.

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Section: Introductionmentioning

confidence: 94%

“…Studies have found that the level of HER2 amplification, in particular the HER2 gene copy number, has been associated with response and survival following HER2-directed NAC. 15 [23][24], However, more studies are needed to determine detailed HER2-specific testing results and correlation with recurrence and survival outcomes after NAC.…”

Section: Introductionmentioning

confidence: 99%

HER2 Testing Characteristics Can Predict Residual Cancer Burden following Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer

Lillemoe

Rendi

Tsai

et al. 2021

International Journal of Breast Cancer

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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%

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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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Is there a correlation between HER2 gene amplification level and response to neoadjuvant treatment with trastuzumab and chemotherapy in HER2-positive breast cancer?

et al. 2021

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Clinicopathologic Factors Associated With Response to Neoadjuvant Anti-HER2–Directed Chemotherapy in HER2-Positive Breast Cancer

Cited by 25 publications

References 24 publications

HER2 Testing Characteristics Can Predict Residual Cancer Burden following Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer

HER2 Testing Characteristics Can Predict Residual Cancer Burden following Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer

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

Is there a correlation between HER2 gene amplification level and response to neoadjuvant treatment with trastuzumab and chemotherapy in HER2-positive breast cancer?

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