Clinical response after two cycles compared to HER2, Ki-67, p53, and bcl-2 in independently predicting a pathological complete response after preoperative chemotherapy in patients with operable carcinoma of the breast

Minckwitz, Gϋnter von; Sinn, Hans‐Peter; Raab, G.; Loibl, Sibylle; Blohmer, Jens-Uwe; Eidtmann, Holger; Hilfrich, J.; Merkle, E.; Jackisch, Christian; Costa, Serban Dan; Caputo, Angelika; Kaufmann, M.

doi:10.1186/bcr1989

Cited by 100 publications

(73 citation statements)

References 27 publications

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“…However, the pCR rate in ER negative tumors was similar in the 2 groups, suggesting that the lack of benefit of additional tamoxifen was not attributable to a detrimental effect of the concomitant administration of the endocrine agent [26].…”

Section: Discussionmentioning

confidence: 93%

“…A pCR rate of about 10% was observed in both groups. In a subset analysis of the study, including 196 patients with available centrally reviewed core biopsies, about 40% of tumors turned out to be ER negative [26]. Patients with ER positive tumors treated with the combination of chemotherapy and tamoxifen had no pCR while 3.5% of pCR was observed in the same subset of tumors treated with chemotherapy alone.…”

Section: Discussionmentioning

confidence: 99%

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Letrozole plus GnRH analogue as preoperative and adjuvant therapy in premenopausal women with ER positive locally advanced breast cancer

Torrisi

Bagnardi

Rotmensz

et al. 2011

Breast Cancer Res Treat

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Purpose:Patients with large ER positive tumors candidate to preoperative chemotherapy may also benefit from a concurrent endocrine intervention, but this issue has been scarcely investigated due to concerns arising from unfavorable results emerged from an adjuvant trial of concurrent tamoxifen and chemotherapy. Patients and Methods:We retrospectively investigated the activity of letrozole plus GnRH analogue (GnRH-a) administered concurrently with preoperative chemotherapy and as adjuvant treatment in premenopausal women with locally advanced ER positive breast cancer consecutively admitted at the European Institute of Oncology. Results were compared with those of a non randomized unmatched control group of premenopausal women with locally advanced ER positive breast cancer receiving preoperative chemotherapy, followed by tamoxifen and GnRH-a after surgery.Primary endpoints were pathological complete response (pCR) rate, decrease of Ki67 and disease free survival (DFS). Results:One-hundred and nineteen women constituted the study group, while 95 patients served as controls. The pCR rate was 5.0% vs 1.1% in the study and control group, respectively. A statistically significant greater suppression of Ki67 was observed in patients receiving chemoendocrine therapy as compared with controls (p=0.003). At a median follow up of 59 months, 26 events occurred in the chemoendocrine group and 48 in the control group. Five-yr DFS was 78% vs 41% in the study and in the control group, respectively [adjusted HR 0.46 95%CI 0.27-0.79, p=.0047]. ConclusionsThe concurrent administration of letrozole and GnRH-a with preoperative chemotherapy was highly effective in premenopausal women with large ER positive breast cancer in terms of decreased proliferation and of improved DFS. Randomized studies are warranted to establish the role of the addition of endocrine therapy to chemotherapy as standard preoperative approach for ER positive locally advanced breast cancer as well as of letrozole in combination with GnRH-a for the treatment of premenopauasal women with early breast cancer.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Letrozole plus GnRH analogue as preoperative and adjuvant therapy in premenopausal women with ER positive locally advanced breast cancer

Torrisi

Bagnardi

Rotmensz

et al. 2011

Breast Cancer Res Treat

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“…Recently we and others showed that the rate of pathological complete remissions (pCR) differs between biologic phenotypes. [1][2][3][4][5] In a smaller subset of the GeparDuo trial [6] patients with a HR+/HER2-had a very low chance of achieving a pCR but had still an excellent prognosis. Whereas patients with HR-/HER2+ tumors have only an excellent prognosis when achieving a pCR.…”

Section: Introductionmentioning

confidence: 99%

Effect of neoadjuvant anthracycline–taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study

Huober

Minckwitz

Denkert

et al. 2010

Breast Cancer Res Treat

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248

146

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Results: The overall pCR rate, defined as no invasive residuals in breast and axilla, was 20.5 %. The highest pCR rate of 57% was observed in patients below 40 years of age with triple negative or grade 3 tumors. Independent factors for mid-course response and pCR were: young age, non-T4 tumors, high grade, and hormone receptor status, the strongest single predictive factor. Within the biological subtypes grading was an independent factor to predict pCR for luminal tumors, clinical tumor stage for the HER2 like tumors and age for the triple negative ones. Grading gave independent information for mid-course response within the triple negative group. No factor predicted mid-course response within the other groups.Conclusion: Grading and age can identify subgroups within the luminal and triple negative patients who have an increased benefit from neoadjuvant chemotherapy.

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“…Immunopositivity for Ki-67 is found in highly proliferative cells, and high Ki-67 immunopositivity is frequently found in poorly differentiated carcinomas. 44,45 Our results showed more nuclear Ki-67 immunoreactivity in tumor model tissues, while those treated with Fe 3 O 4 -MNP-DDP showed lower nuclear Ki-67 immunoreactivity, indicating that Fe 3 O 4 -MNP-DDP can inhibit cell proliferation and tumor growth. Further, other researchers have shown that overexpression of LRP in a subgroup of cisplatin-resistant NSCLC cell lines plays an important role in drug resistance, in which involved the NSCLC cells from toxic impacts of cisplatin by intrinsic mechanism.…”

Section: Discussionmentioning

confidence: 75%

Reversal of multidrug resistance by cisplatin-loaded magnetic Fe3O4 nanoparticles in A549/DDP lung cancer cells in vitro and in vivo

Chen²,

Xu³

et al. 2013

IJN

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Abstract:The purpose of this study was to explore whether magnetic Fe 3 O 4 nanoparticles (Fe 3 O 4 -MNP) loaded with cisplatin (Fe 3 O 4 -MNP-DDP) can reverse DDP resistance in lung cancer cells and to investigate mechanisms of multidrug resistance in vitro and in vivo. MTT assay showed that DDP inhibited both A549 cells and DDP-resistant A549 cells in a timedependent and dose-dependent manner, and that this inhibition was enhanced by Fe 3 O 4 -MNP. An increased rate of apoptosis was detected in the Fe 3 O 4 -MNP-DDP group compared with a control group and the Fe 3 O 4 -MNP group by flow cytometry, and typical morphologic features of apoptosis were confirmed by confocal microscopy. Accumulation of intracellular DDP in the Fe 3 O 4 -MNP-DDP group was greater than that in the DDP group by inductively coupled plasma mass spectrometry. Further, lower levels of multidrug resistance-associated protein-1, lung resistance-related protein, Akt, and Bad, and higher levels of caspase-3 genes and proteins, were demonstrated by reverse transcriptase polymerase chain reaction and Western blotting in the presence of Fe 3 O 4 -MNP-DDP. We also demonstrated that Fe 3 O 4 -MNP enhanced the effect of DDP on tumor growth in BALB/c nude mice bearing DDP-resistant human A549 xenografts by decreasing localization of lung resistance-related protein and Ki-67 immunoreactivity in cells. There were no apparent signs of toxicity in the animals. Overall, these findings suggest potential clinical application of Fe 3 O 4 -MNP-DDP to increase cytotoxicity in lung tumor xenografts.

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Clinical response after two cycles compared to HER2, Ki-67, p53, and bcl-2 in independently predicting a pathological complete response after preoperative chemotherapy in patients with operable carcinoma of the breast

Abstract: Background To investigate the predictive value of clinical and biological markers for a pathological complete remission after a preoperative dose-dense regimen of doxorubicin and docetaxel, with or without tamoxifen, in primary operable breast cancer.

Cited by 100 publications

References 27 publications

Letrozole plus GnRH analogue as preoperative and adjuvant therapy in premenopausal women with ER positive locally advanced breast cancer

Letrozole plus GnRH analogue as preoperative and adjuvant therapy in premenopausal women with ER positive locally advanced breast cancer

Effect of neoadjuvant anthracycline–taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study

Reversal of multidrug resistance by cisplatin-loaded magnetic Fe3O4 nanoparticles in A549/DDP lung cancer cells in vitro and in vivo

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