Predicting Early Failure after Adjuvant Chemotherapy in High-Risk Breast Cancer Patients with Extensive Lymph Node Involvement

Faneyte, Ian F.; Peterse, Johannes L.; Tinteren, Harm van; Pronk, C.; Bontenbal, Marijike; Beex, L.V.A.M.; Wall, Elsken van der; Richel, Dick J.; Nooij, M.; Voest, Emile E.; Hupperets, P.; Vergert, E.M. Ten; Vries, Elisabeth G.E. de; Rodenhuis, S.; Vijver, Marc J. van de

doi:10.1158/1078-0432.ccr-03-0054

Cited by 39 publications

(22 citation statements)

References 30 publications

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“…While the clinical course is highly variable, up to onethird of the patients with stage I and II disease are expected to experience recurrence [3]. Metastatic breast cancer remains an incurable disease.…”

Section: Introductionmentioning

confidence: 99%

Concomitant docetaxel plus gemcitabine versus sequential docetaxel followed by gemcitabine in anthracycline-pretreated metastatic or locally recurrent inoperable breast cancer patients: a prospective multicentre trial of the Central European Cooperative Oncology Group (CECOG)

Tomova¹,

Bartsch

Brodowicz

et al. 2009

Breast Cancer Res Treat

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Docetaxel (D) plus gemcitabine (G) is an active combination in anthracycline pre-treated breast cancer. Impact of sequential administration of these drugs is unclear. This trial aimed to compare concomitant DG with sequential D ? G. Patients were randomised to eight cycles of gemcitabine 1,000 mg/m 2 on days 1 ? 8 plus docetaxel 75 mg/ m 2 on day 8, or 4 cycles of docetaxel 100 mg/m 2 on day 1, followed by four cycles of gemcitabine 1,250 mg/m 2 on days 1 ? 8, in a 21-day schedule. Time to progression (TTP) was defined as primary endpoint; secondary endpoints were overall response rate (ORR), response duration (RD), overall survival (OS) and toxicity. Due to poor recruitment, the trial was terminated after 100 of a pre-planned 430 patients. Patient characteristics were well balanced. No significant difference was observed in terms of TTP, ORR, RD and OS. Grade 3/4 adverse events encompassed leucopoenia (29 vs. 68%, P \ 0.001), neutropoenia (49 vs. 83%, P \ 0.001) and febrile neutropoenia (4 vs. 9%, n.s.), all favouring D ? G. No difference in efficacy was observed between concomitant and sequential treatment. D ? G produced significantly more episodes of haematological toxicity due to the administration of docetaxel at 100 mg/m 2 without GCSFsupport.

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Section: Introductionmentioning

confidence: 99%

Concomitant docetaxel plus gemcitabine versus sequential docetaxel followed by gemcitabine in anthracycline-pretreated metastatic or locally recurrent inoperable breast cancer patients: a prospective multicentre trial of the Central European Cooperative Oncology Group (CECOG)

Tomova¹,

Bartsch

Brodowicz

et al. 2009

Breast Cancer Res Treat

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“…Although the clinical course of disease is highly variable, up to one third of patients with stage I and II disease are expected to experience tumor recurrence (3). Metastatic breast cancer remains an incurable disease.…”

mentioning

confidence: 99%

Her2 and Progesterone Receptor Status Are Not Predictive of Response to Fulvestrant Treatment

Bartsch

Wenzel

Altorjai

et al. 2007

Clinical Cancer Research

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Purpose: It has been hypothesized that response to endocrine therapy for breast cancer depends on Her2 and progesterone receptor status, grading, and tumor proliferation rate. In this study, we evaluated factors that are potentially predictive of response and time to progression in patients treated with fulvestrant. Experimental Design: One hundred fifty-five patients were included and followed prospectively. Patients received fulvestrant at standard dose by i.m. injection. Response was evaluated every 3 months using International Union Against Cancer criteria. Time to progression and overall survival were estimated with the Kaplan-Meier product limit method. A multivariate analysis was done to evaluate factors potentially influencing response and time to progression. Results: We observed a partial response in 19 patients (12.3%), stable disease z6 months in 56 patients (36.1%), stable disease >3 months but <6 months in 7 patients (4.5%), and progressive disease in 73 patients (47.1%). Median time to progression was 5 months, and median overall survival was 27 months. Probability of achieving clinical benefit was significantly associated with a low proliferation rate (P = 0.015), nonvisceral metastatic sites (P = 0.023), and first-line therapy (P = 0.023). First-line therapy was also associated with prolonged time to progression (P = 0.003). Conclusions: Response rate and time to progression are shown to be independent of Her2 status, grading, and progesterone receptor status.This is probably caused by the unique mechanism of action associated with fulvestrant: Due to receptor down-regulation, it blocks nuclear, cytoplasmatic, and membrane-bound estrogen receptor. Therefore, it seems to inhibit the cross-talk between growth factor receptor signaling and estrogen receptor in a more effective manner.

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“…25 Most metastatic disease will progress within one year of beginning treatment, and recurrence has been observed with early breast cancer following adjuvant trastuzumab therapy. 23,24,26,27 Although effective in inhibiting metastasis to the liver, lymph nodes, and bone, trastuzumab is associated with an increase in risk of central nervous system metastasis as a site of first tumor recurrence. Finally, incidences of cardiotoxicity had been observed in the pivotal Phase III trial evaluating trastuzumab in combination with chemotherapy.…”

Section: Anti-erbb2 Therapies For Breast Cancermentioning

confidence: 99%

Lapatinib: new opportunities for management of breast cancer

Lee¹,

Gallas²,

Pegram³

et al. 2010

BCTT

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Approximately 20% of new diagnosed breast cancers overexpress the human epidermal growth factor receptor 2 (EGFR2), also known as erythroblastic leukemia viral oncogene homolog 2 (ERBB2) protein, as a consequence of ERBB2 gene amplification, resulting in a poor prognosis. Clinical outcome can be substantially improved by ERBB2-targeted therapy. Lapatinib is a potent, orally bioavailable small molecule that reversibly and selectively inhibits epidermal growth factor receptor (EGFR1 or ERBB1) and ERBB2 tyrosine kinases. Lapatinib binds the adenosine triphosphate-binding site of the receptor's intracellular domain to inhibit tumor cell growth. This review summarizes the pharmacology, pharmacokinetics, efficacy, and tolerability of lapatinib, and reviews both Food and Drug Administration-approved and investigational uses of lapatinib in breast cancer therapy. The drug is generally well tolerated in patients, with diarrhea and rashes being the most common (usually mild or moderate) adverse effects. Unlike trastuzumab, lapatinib has infrequent adverse effects on cardiac function. Lapatinib has substantial activity for advanced ERBB2-positive breast cancer, particularly in combination with capecitabine, following progression after anthracyclines, taxanes, and trastuzumab. Lapatinib combined with capecitabine yielded significant improvements in time to progression and response rate compared with capecitabine alone. This drug can also be combined with letrozole for the treatment of postmenopausal women with ERBB2-positive breast cancer, for whom hormonal therapy is indicated. Lapatinib has shown early promise in treatment of central nervous system metastasis and is being further evaluated in various clinical settings.

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Predicting Early Failure after Adjuvant Chemotherapy in High-Risk Breast Cancer Patients with Extensive Lymph Node Involvement

Cited by 39 publications

References 30 publications

Concomitant docetaxel plus gemcitabine versus sequential docetaxel followed by gemcitabine in anthracycline-pretreated metastatic or locally recurrent inoperable breast cancer patients: a prospective multicentre trial of the Central European Cooperative Oncology Group (CECOG)

Concomitant docetaxel plus gemcitabine versus sequential docetaxel followed by gemcitabine in anthracycline-pretreated metastatic or locally recurrent inoperable breast cancer patients: a prospective multicentre trial of the Central European Cooperative Oncology Group (CECOG)

Her2 and Progesterone Receptor Status Are Not Predictive of Response to Fulvestrant Treatment

Lapatinib: new opportunities for management of breast cancer

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