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1.  Gross cystic disease fluid protein 15 (GCDFP-15) expression in breast cancer subtypes 
BMC Cancer  2014;14(1):546.
Background
Gross cystic disease fluid protein 15 (GCDFP-15), which is regulated by the androgen receptor (AR), is a diagnostic marker for mammary differentiation in histopathology. We determined the expression of GCDFP-15 in breast cancer subtypes, its potential prognostic and predictive value, as well as its relationship to AR expression.
Methods
602 pre-therapeutic breast cancer core biopsies from the phase III randomized neoadjuvant GeparTrio trial (NCT00544765) were investigated for GCDFP-15 expression by immunohistochemistry. Expression data were correlated with disease-free (DFS) and overall survival (OS) time as well as pathological complete response (pCR) to neoadjuvant chemotherapy.
Results
239 tumors (39.7%) were GCDFP-15 positive. GCDFP-15 expression was positively linked to hormone receptor (HR) and HER2 positive tumor type, while most triple negative carcinomas were negative (p < 0.0001). GCDFP-15 was also strongly correlated to AR expression (p 0.001), and to the so-called molecular apocrine subtype (HR-/AR+, p < 0.0001). Higher rates of GCDFP-15 positivity were seen in tumors of lower grade (<0.0001) and negative nodal status (p = 0.008). GCDFP-15 positive tumors tended to have a more favourable prognosis than GCDFP-15 negative tumors (DFS (p = 0.052) and OS (p = 0.044)), which was not independent from other factors in multivariate analysis. GCDFP-15 expression was not linked to pCR. Histological apocrine differentiation was frequent in molecular apocrine carcinomas (60.7%), and was associated with GCDFP-15 within this group (p = 0.039).
Conclusions
GCDFP-15 expression is higher in tumors with favorable prognostic features. GCDFP-15 expression is further a frequent feature of AR positive tumors and the molecular apocrine subtype. It might have reduced sensitivity as a diagnostic marker for mammary differentiation in triple negative tumors as compared to HR or HER2 positive tumor types.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2407-14-546) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2407-14-546
PMCID: PMC4122770  PMID: 25070172
GCDFP-15; Breast cancer; Neoadjuvant chemotherapy; Apocrine; CUP
2.  Adjuvant Therapy With Zoledronic Acid in Patients With Breast Cancer: A Systematic Review and Meta-Analysis 
The Oncologist  2013;18(4):353-361.
A systematic review and meta-analysis of randomized clinical trials estimating the impact on survival outcomes and fracture rates of the use of zoledronic acid versus no use (or delayed use) in the adjuvant treatment of early-stage breast cancer patients is presented.
Background.
The purpose of the study was to estimate the impact on survival and fracture rates of the use of zoledronic acid versus no use (or delayed use) in the adjuvant treatment of patients with early-stage (stages I–III) breast cancer.
Materials and Methods.
We performed a systematic review and meta-analysis of randomized clinical trials. Trials were located through PubMed, ISI, Cochrane Library, and major cancer scientific meeting searches. All trials that randomized patients with primary breast cancer to undergo adjuvant treatment with zoledronic acid versus nonuse, placebo, or delayed use of zoledronic acid as treatment to individuals who develop osteoporosis were considered eligible. Standard meta-analytic procedures were used to analyze the study outcomes.
Results.
Fifteen studies were considered eligible and were further analyzed. The use of zoledronic acid resulted in a statistically significant better overall survival outcome (five studies, 6,414 patients; hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.70–0.94). No significant differences were found for the disease-free survival outcome (seven studies, 7,541 patients; HR, 0.86; 95% CI, 0.70–1.06) or incidence of bone metastases (seven studies, 7,543 patients; odds ratio [OR], 0.94; 95% CI, 0.64–1.37). Treatment with zoledronic acid led to a significantly lower overall fracture rate (OR, 0.78; 95% CI, 0.63–0.96). Finally, the rate of osteonecrosis of the jaw was 0.52%.
Conclusion.
Zoledronic acid as adjuvant therapy in breast cancer patients appears to not only reduce the fracture risk but also offer a survival benefit over placebo or no treatment.
doi:10.1634/theoncologist.2012-0261
PMCID: PMC3639520  PMID: 23404816
Zoledronic acid; Adjuvant; Breast cancer; Bisphosphonates
3.  Re-Challenging Taxanes in Recurrent Breast Cancer in Patients Treated with (Neo-)Adjuvant Taxane-Based Therapy 
Breast Care  2011;6(4):279-283.
Summary
Background: Docetaxel and paclitaxel are among the most active substances for the treatment of breast cancer. As both drugs are used today in adjuvant regimens, efficacy data from pivotal trials in the metastatic setting in taxane-naive populations cannot reliably be used as references. Patients and Methods: The Taxane Re-Challenge Cohort Study identified participants from 6 prospective (neo-)adjuvant taxane-based studies with recurrent disease and collected data on their subsequent treatment. Out of 381 recurrent patients, 106 (27.8%) were re-challenged with a taxane-based treatment as first- or later-line therapy for recurrent disease. Results: Taxanes were used as first-line therapy in 74 patients and showed a response rate of 48.6% (including complete responses in 27.0%). The response rate was dependent on the disease-free interval (<1 year: 34.8%; 1-2 years: 42.9%; >2 years: 63.3%; p = 0.04) and visceral metastasis (present: 62.5%; not present 32.4%; p = 0.01). Patients without visceral metastasis and with a disease-free interval of >2 years achieved the longest overall survival. Hormone and HER2 receptor status were not predictive; however, triple-negative tumors responded in 50.0%. The overall response rate of later-line taxane-based treatment was 28.2%. Conclusion: Re-challenging taxanes appears to be effective and therefore represents a reasonable option in this population.
doi:10.1159/000330946
PMCID: PMC3225212  PMID: 22164126
Docetaxel; Paclitaxel; Adjuvant; Recurrent breast cancer
4.  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 
Introduction
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.
Methods
Patients with a histologically confirmed diagnosis of previously untreated, operable, and measurable primary breast cancer (tumour (T), nodes (N) and metastases (M) score: T2-3(≥ 3 cm) N0-2 M0) were treated in a prospectively randomised trial with four cycles of dose-dense (bi-weekly) doxorubicin and docetaxel (ddAT) chemotherapy, with or without tamoxifen, prior to surgery. Clinical and pathological parameters (menopausal status, clinical tumour size and nodal status, grade, and clinical response after two cycles) and a panel of biomarkers (oestrogen and progesterone receptors, Ki-67, human epidermal growth factor receptor 2 (HER2), p53, bcl-2, all detected by immunohistochemistry) were correlated with the detection of a pathological complete response (pCR).
Results
A pCR was observed in 9.7% in 248 patients randomised in the study and in 8.6% in the subset of 196 patients with available tumour tissue. Clinically negative axillary lymph nodes, poor tumour differentiation, negative oestrogen receptor status, negative progesterone receptor status, and loss of bcl-2 were significantly predictive for a pCR in a univariate logistic regression model, whereas in a multivariate analysis only the clinical nodal status and hormonal receptor status provided significantly independent information. Backward stepwise logistic regression revealed a response after two cycles, with hormone receptor status and lymph-node status as significant predictors. Patients with a low percentage of cells stained positive for Ki-67 showed a better response when treated with tamoxifen, whereas patients with a high percentage of Ki-67 positive cells did not have an additional benefit when treated with tamoxifen. Tumours overexpressing HER2 showed a similar response to that in HER2-negative patients when treated without tamoxifen, but when HER2-positive tumours were treated with tamoxifen, no pCR was observed.
Conclusion
Reliable prediction of a pathological complete response after preoperative chemotherapy is not possible with clinical and biological factors routinely determined before start of treatment. The response after two cycles of chemotherapy is a strong but dependent predictor. The only independent factor in this subset of patients was bcl-2.
Trial registration number
NCT00543829
doi:10.1186/bcr1989
PMCID: PMC2397529  PMID: 18380893

Results 1-4 (4)