Predictive value of apoptosis, proliferation, HER-2, and topoisomerase IIα for anthracycline chemotherapy in locally advanced breast cancer

Arpino, Grazia; Ciocca, Daniel R.; Weiss, Heidi L.; Allred, D. Craig; Daguerre, Pedro; Vargas–Roig, Laura M.; Leuzzi, Marcela; Gago, Francisco E.; Elledge, Richard M.; Mohsin, Syed K.

doi:10.1007/s10549-005-1721-9

Cited by 45 publications

(41 citation statements)

References 29 publications

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“…Anthracycline derivatives, such as the doxorubicin used in this trial, have been found to induce both an early increase in apoptotic activity and a decrease in proliferation (35). We expect that cellular assays will correlate with DOS functional measurements of biochemical changes within 1 week posttherapy.…”

Section: Discussionmentioning

confidence: 89%

Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy

Cerussi

Hsiang

Shah

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

276

259

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Diffuse optical spectroscopy (DOS) and imaging are emerging diagnostic techniques that quantitatively measure the concentration of deoxy-hemoglobin (ctHHb), oxy-hemoglobin (ctO 2Hb), water (ctH 2O), and lipid in cm-thick tissues. In early-stage clinical studies, diffuse optical imaging and DOS have been used to characterize breast tumor biochemical composition and monitor therapeutic response in stage II/III neoadjuvant chemotherapy patients. We investigated whether DOS measurements obtained before and 1 week into a 3-month adriamycin/cytoxan neoadjuvant chemotherapy regimen can predict final, postsurgical pathological response. Baseline DOS measurements of 11 patients before therapy revealed significant increases in tumor ctHHb, ctO 2Hb, ctH 2O, and spectral scattering slope, and decreases in bulk lipids, relative to normal breast tissue. Tumor concentrations of ctHHb, ctO 2Hb, and ctH2O dropped 27 ؎ 15%, 33 ؎ 7%, and 11 ؎ 15%, respectively, within 1 week (6.5 ؎ 1.4 days) of the first treatment for pathology-confirmed responders (n ‫؍‬ 6), whereas nonresponders (n ‫؍‬ 5) and normal side controls showed no significant changes in these parameters. The best single predictor of therapeutic response 1 week posttreatment was ctHHb (83% sensitivity, 100% specificity), while discrimination analysis based on combined ctHHb and ctH 2O changes classified responders vs. nonresponders with 100% sensitivity and specificity. In addition, the pretreatment tumor-to-normal ctO 2Hb ratio was significantly higher in responders (2.82 ؎ 0.44) vs. nonresponders (1.82 ؎ 0.49). These results highlight DOS sensitivity to tumor cellular metabolism and biochemical composition and demonstrate its potential for predicting and monitoring an individual's response to treatment.diffuse optical imaging ͉ frequency-domain photon migration ͉ near-infrared ͉ tissue spectroscopy ͉ translational research O ptimal management locally advanced breast cancer (LABC) remains a complex therapeutic problem (1). LABC represents 5-20% of all newly diagnosed breast cancers in the United States with a higher incidence in medically underserved areas (2). Treatment for LABC has evolved from radical mastectomy to preoperative neoadjuvant chemotherapy followed by mastectomy or breast conservation therapy (3). Despite aggressive local therapy, long-term patient survival is still poor. LABC remains controversial because of uncertainties in determining the optimal intensity and duration of neoadjuvant chemotherapy and evaluating therapeutic response (2, 4, 5).Neoadjuvant chemotherapy response is determined by serial physical examination, mammography and/or ultrasound. Complete pathological response (cPR) is an important therapeutic endpoint that is a surrogate for eradicating micrometastases, and strongly correlates with patient survival (6). Thus one goal of neoadjuvant chemotherapy monitoring is to determine early when a patient will demonstrate cPR. Many studies revealed significant discrepancies between clinical response assessments and final pathology (7-9).A rece...

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Section: Discussionmentioning

confidence: 89%

Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy

Cerussi

Hsiang

Shah

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

276

259

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“…Analyzing data from the literature on TOP2A status and its role as a predictive factor in invasive breast carcinoma is a confusing experience [18][19][20][21][22][23]. Outcomes of results both at the level of evaluation of TOP2A as well as at the level of interpretation are extremely different [24][25][26][27][28][29][30][31][32][33].…”

Section: Discussionmentioning

confidence: 99%

Topoisomerase 2α status in invasive breast carcinoma – comparison of its clinical value according to immunohistochemical and fluorescence in situ hybridization methods of evaluation

Olszewski¹,

Pieńkowski²,

Olszewski³

et al. 2014

pjp

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The main purpose of the study was to compare topoisomerase 2α (TOP2A) status in invasive breast carcinomas to the outcome of a therapy containing neoadjuvant treatment with anthracyclines (a combination chemotherapy treatment for breast cancer, namely AC [cyclophosphamide, doxorubicin]). To achieve these goals we created a method of evaluation with criteria based on two methods used in the present study (immunohistochemical [IHC] and fluorescence in situ hybridization [FISH]). The threshold for positive immunohistochemically evaluated status was set for all cases with: nuclear stain intensity score 3+ in 10% or more nuclei and nuclear stain intensity score 2+ in 50% or more nuclei. Our results suggest that TOP2A status may be used as a predictive factor for patient selection for protocols which include anthracyclines as one of the chemotherapeutics. Both methods, IHC and FISH, are suitable for implementation for diagnostic purposes, but IHC positive status measured according to the criteria presented above is the best predictor of longer disease-free survival (DFS) according to our study. Immunohistochemical also gave satisfactory results in all analyzed cases in comparison to only 60% of cases analyzed by FISH.

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“…However, de novo and acquired resistance to therapy is observed in a significant subset of patients, leading to subsequent disease progression [149]. In contrast to predictive factors for targeted therapy, predictive markers for chemosensitivity are less well-defined [150,151]. Chemotherapy agents including CMF, taxanes and anthracycline-based chemotherapy affect cell division or DNA synthesis and function in some way.…”

Section: Proliferation Markersmentioning

confidence: 99%

“…Other markers that have been used as a predictor of outcome and response to therapy include Topoisomerase II alpha expression and (TOP2A) gene amplification (molecular target for anthracyclines) [98,150,163], Bcl2 and p53 expression [164,165]. TOP2A aberrations (amplification, deletion) are found in up to approximately 30-90% of HER2-amplified BC, and amplifications are more common than deletions.…”

Section: Additional Markersmentioning

confidence: 99%

Combinatorial biomarker expression in breast cancer

Rakha

Reis‐Filho

Ellis

2010

Breast Cancer Res Treat

190

144

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Current clinical management of breast cancer relies on the availability of robust clinicopathological variables and few well-defined biological markers. Recent microarray-based expression profiling studies have emphasised the importance of the molecular portraits of breast cancer and the possibility of classifying breast cancer into biologically and molecularly distinct groups. Subsequent large scale immunohistochemical studies have demonstrated that the added value of studying the molecular biomarker expression in combination rather than individually. Oestrogen (ER) and progesterone (PR) receptors and HER2 are currently used in routine pathological assessment of breast cancer. Additional biomarkers such as proliferation markers and 'basal' markers are likely to be included in the future. A better understanding of the prognostic and predictive value of combinatorial assessment of biomarker expression could lead to improved breast cancer management in routine clinical practice and would add to our knowledge concerning the variation in behaviour and response to therapy. Here, we review the evidence on the value of assessing biomarker expression in breast cancer individually and in combination and its relation to the recent molecular classification of breast cancer.

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Predictive value of apoptosis, proliferation, HER-2, and topoisomerase IIα for anthracycline chemotherapy in locally advanced breast cancer

Cited by 45 publications

References 29 publications

Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy

Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy

Topoisomerase 2α status in invasive breast carcinoma – comparison of its clinical value according to immunohistochemical and fluorescence in situ hybridization methods of evaluation

Combinatorial biomarker expression in breast cancer

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