Phenotypic and proteomic alterations of acquired trastuzumab resistance

Tripathy, Debu; Hassan, Saima; Verma, Udit; Gurnani, Pooja; Nandi, Ajeya; Rosenblatt, Kevin P.

doi:10.1200/jco.2005.23.16_suppl.3121

Cited by 9 publications

(5 citation statements)

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“…The effectiveness of trastuzumab in metastatic breast cancer as well as the remarkable reduction in relapse among HER2-positive breast cancers treated with trastuzumab combined with chemotherapy supports the idea that effective tumor control can be achieved with isolated targeting of this pathway 22-24 but not all HER2-positive tumors respond to trastuzumab. PTEN loss or abrogation, 25 and CXCR4 upregulation 26 have been implicated in trastuzumab resistance and may provide targets for combination strategies for even better approaches in the future.…”

Section: Treatment Response and Outcomementioning

confidence: 99%

Molecular Classification and Molecular Forecasting of Breast Cancer: Ready for Clinical Application?

Brenton

Carey

Ahmed

et al. 2005

JCO

830

636

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Profiling breast cancer with expression arrays has become common, and it has been suggested that the results from early studies will lead to understanding of the molecular differences between clinical cases and allow individualization of care. We critically review two main applications of expression profiling; studies unraveling novel breast cancer classifications and those that aim to identify novel markers for prediction of clinical outcome. Breast cancer may now be subclassified into luminal, basal, and HER2 subtypes with distinct differences in prognosis and response to therapy. However, profiling studies to identify predictive markers have suffered from methodologic problems that prevent general application of their results. Future work will need to reanalyze existing microarray data sets to identify more representative sets of candidate genes for use as prognostic signatures and will need to take into account the new knowledge of molecular subtypes of breast cancer when assessing predictive effects.

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Section: Treatment Response and Outcomementioning

confidence: 99%

Molecular Classification and Molecular Forecasting of Breast Cancer: Ready for Clinical Application?

Brenton

Carey

Ahmed

et al. 2005

JCO

830

636

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“…More recent preclinical experimental data are contradictory in this regard. Tripathy and colleagues [ 11 ] suggest that breast cancer cell proliferation is inhibited partially by continuing trastuzumab treatment even after the development of resistance to the drug. Similarly, Shirane and colleagues [ 12 ] show that retaining trastuzumab therapy improves the cytotoxic effect of taxanes against trastuzumab-resistant xenografts in nude mice.…”

Section: Introductionmentioning

confidence: 99%

Continuing trastuzumab beyond disease progression: outcomes analysis in patients with metastatic breast cancer

et al. 2008

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“…The long‐term tolerability of the drug as well as the pre‐clinical evidence of additive and, in some cases, synergistic effects obtained when trastuzumab is combined with several cytotoxics (8,9), account for the widespread practice of many oncologists to administer successive trastuzumab‐based lines beyond progression. In support of this behavior, pre‐clinical evidence suggests that the growth ratio of trastuzumab‐resistant cell lines is threefold slower when trastuzumab is maintained (10). More interestingly, another pre‐clinical study demonstrated that, in mice bearing trastuzumab‐resistant tumors, the addition of paclitaxel or docetaxel to trastuzumab resulted in improved anti‐tumor activity as compared with either taxane alone (11).…”

mentioning

confidence: 97%

Time to First Tumor Progression as Outcome Predictor of a Second Trasuzumab-Based Therapy beyond Progression in HER-2 Positive Metastatic Breast Cancer

Metro¹,

Giannarelli²,

Gemma³

et al. 2010

The Breast Journal

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In a previous analysis performed on a cohort of 37 HER-2 positive metastatic breast cancer (MBC) patients treated with trastuzumab beyond progression, we found that a second trastuzumab-based therapy is associated with a considerable response rate and preserved time to progression as compared with a first trastuzumab-based therapy. In the present study, we extended the analysis to a total of 69 patients treated in four different italian Institutions, also trying to identify clinical predictors of sensitivity to a second trastuzumab-based therapy beyond progression. Efficacy results on the overall population confirmed that a second trastuzumab-based therapy beyond progression is an active regimen (27.5% of responses and 6.5 months of time to progression, respectively). Median time to progression to the first trastuzumab therapy (TTP1) identified two groups of patients with different sensitivity to trastuzumab beyond progression (group A, TTP1 >or= 8 months and group B, TTP1 < 8 months) in terms of time to second progression and post-progression survival (group A versus group B showed respectively a time to second progression of 7.6 versus 4.7 months, p = 0.05, and a post-progression survival of 31.7 months versus 21.8 months, p = 0.04). In the multivariate analysis, only TTP1 was a predictor of time to second progression and post-progression survival. Despite the recent approval of lapatinib plus capecitabine for trastuzumab-progressing patients, it is still reasonable to offer trastuzumab beyond progression to HER-2 positive MBC patients, because these data confirm the potential utility of such a conduct. In the clinic, time to first tumor progression may represent a useful tool to identify patients who are more likely to benefit from trastuzumab beyond progression.

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Phenotypic and proteomic alterations of acquired trastuzumab resistance

Cited by 9 publications

References 0 publications

Molecular Classification and Molecular Forecasting of Breast Cancer: Ready for Clinical Application?

Molecular Classification and Molecular Forecasting of Breast Cancer: Ready for Clinical Application?

Continuing trastuzumab beyond disease progression: outcomes analysis in patients with metastatic breast cancer

Time to First Tumor Progression as Outcome Predictor of a Second Trasuzumab-Based Therapy beyond Progression in HER-2 Positive Metastatic Breast Cancer

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