112 research outputs found
Optimising preoperative systemic therapy for breast cancer
This thesis was divided in two parts. Part I demonstrated benefit of zoledronic acid addition to chemotherapy in terms of pathological response in postmenopausal women. Part II is all about neoadjuvant endocrine therapy, and discusses the optimal duration of this treatment and the information on treatment efficacy that aromatase-inhibitor specific adverse events may provide.The printing of this thesis was made possible by the departments of Medical Oncology and Surgery of the Leiden Universtity Medical Center, Boehringer Ingelheim, Chipsoft, Philips, Novartis, Pfizer and Galephar.UBL - phd migration 201
Effects of neoadjuvant chemotherapy with or without zoledronic acid on pathological response: A meta-analysis of randomised trials
Purpose The addition of bisphosphonates to adjuvant therapy improves survival in postmenopausal breast cancer (BC) patients. We report a meta-analysis of four randomised trials of neoadjuvant chemotherapy (CT) +/â zoledronic acid (ZA) in stage II/III BC to investigate the potential for enhancing the pathological response. Methods Individual patient data from four prospective randomised clinical trials reporting the effect of the addition of ZA on the pathological response after neoadjuvant CT were pooled. Primary outcomes were pathological complete response in the breast (pCRb) and in the breast and lymph nodes (pCR). Trial-level and individual patient data meta-analyses were done. Predefined subgroup-analyses were performed for postmenopausal women and patients with triple-negative BC. Results pCRb and pCR data were available in 735 and 552 patients respectively. In the total study population ZA addition to neoadjuvant CT did not increase pCRb or pCR rates. However, in postmenopausal patients, the addition of ZA resulted in a significant, near doubling of the pCRb rate (10.8% for CT only versus 17.7% with CT+ZA; odds ratio [OR] 2.14, 95% confidence interval [CI] 1.01â4.55) and a non-significant benefit of the pCR rate (7.8% for CT only versus 14.6% with CT+ZA; OR 2.62, 95% CI 0.90â7.62). In patients with triple-negative BC a trend was observed favouring CT+ZA. Conclusion This meta-analysis shows no impact from the addition of ZA to neoadjuvant CT on pCR. However, as has been seen in the adjuvant setting, the addition of ZA to neoadjuvant CT may augment the effects of CT in postmenopausal patients with BC
Estrogen Receptor pathway activity score to predict clinical response or resistance to neo-adjuvant endocrine therapy in primary breast cancer
The prognostic and predictive value of Tregs and tumor immune subtypes in postmenopausal, hormone receptor-positive breast cancer patients treated with adjuvant endocrine therapy: a Dutch TEAM study analysis
Evidence exists for an immunomodulatory effect of endocrine therapy in hormone receptor-positive (HR+ve) breast cancer (BC). Therefore, the aim of this study was to define the prognostic and predictive value of tumor immune markers and the tumor immune profile in HR+ve BC, treated with different endocrine treatment regimens. 2,596 Dutch TEAM patients were treated with 5 years of adjuvant hormonal treatment, randomly assigned to different regimens: 5 years of exemestane or sequential treatment (2.5 years of tamoxifenâ2.5 years of exemestane). Immunohistochemistry was performed for HLA class I, HLA-E, HLA-G, and FoxP3. Tumor immune subtypes (IS) (low, intermediate & high immune susceptible) were determined by the effect size of mono-immune markers on relapse rate. Patients on sequential treatment with high level of tumor-infiltrating FoxP3+ cells had significant (p = 0.019, HR 0.729, 95 % CI 0.560â0.949) better OS. Significant interaction for endocrine treatment and FoxP3+ presence was seen (OS p < 0.001). Tumor IS were only of prognostic value for the sequentially endocrine-treated patients (RFP: p = 0.035, HR intermediate IS 1.420, 95 % CI 0.878â2.297; HR low IS 1.657, 95 % CI 1.131â2.428; BCSS: p = 0.002, HR intermediate IS 2.486, 95 % CI 1.375â4.495; HR low IS 2.422, 95 % CI 1.439â4.076; and OS: p = 0.005, HR intermediate IS 1.509, 95 % CI 0.950â2.395; HR low IS 1.848, 95 % CI 1.277â2.675). Tregs and the tumor IS presented in this study harbor prognostic value for sequentially endocrine-treated HR+ve postmenopausal BC patients, but not for solely exemestane-treated patients. Therefore, these markers could be used as a clinical risk stratification tool to guide adjuvant treatment in this BC population
Trends in the distribution of gestational age and contribution of planned births in New South Wales, Australia
§<p>Relative change was calculated by: [(2009 rate â1994 rate)/(1994 rate)].</p>*<p>100; Test-for-trend was significant for all factors except stillbirths and multiple births, P<0.001.</p>â <p>Low risk pregnancies defined as primiparae, aged 20â34 years, without pregnancy complications; and with a liveborn singleton infant, born in cephalic presentation and of normal fetal growth at the 10<sup>th</sup>â90th birth weight percentile of the distribution for gestational age and infant sex. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056238#pone.0056238-Cheng1" target="_blank">[16]</a>.</p>*<p>Numbers may not add up to totals due to missing data or rounding.</p
Tumor-stroma ratio is associated with Miller-Payne score and pathological response to neoadjuvant chemotherapy in HER2-negative early breast cancer
The tumor-stroma ratio (TSR) has proven to be a strong prognostic factor in breast cancer, demonstrating better survival for patients with stroma-low tumors. Since the role of the TSR as a predictive marker for neoadjuvant chemotherapy outcome is yet unknown, this association was evaluated for HER2-negative breast cancer in the prospective DIRECT and NEOZOTAC trials. The TSR was assessed on 375 hematoxylin and eosin-stained sections of pre-treatment biopsies. Associations between the TSR and chemotherapy response according to the Miller-Payne (MP) grading system, and between the TSR and pathological response were examined using Pearson's chi-square, Cochran-Armitage test for trend and regression analyses. A stroma-low tumor prior to neoadjuvant chemotherapy was significantly associated with a higher MP score (P = .005). This relationship remained significant in the estrogen receptor (ER)-negative subgroup (P = .047). The univariable odds ratio (OR) of a stroma-low tumor on pathological complete response (pCR) was 2.46 (95% CI 1.34-4.51, P = .004), which attenuated to 1.90 (95% CI 0.85-4.25, P = .119) after adjustment for relevant prognostic factors. Subgroup analyses revealed an OR of 5.91 in univariable analyses for ER-negativity (95% CI 1.19-29.48, P = .030) and 1.48 for ER-positivity (95% CI 0.73-3.01, P = .281). In conclusion, a low amount of stroma on pre-treatment biopsies is associated with a higher MP score and pCR rate. Therefore, the TSR is a promising biomarker in predicting neoadjuvant treatment outcome. Incorporating this parameter in routine pathological diagnostics could be worthwhile to prevent overtreatment and undertreatment.Surgical oncolog
Comparative study of neoadjuvant chemotherapy with and without Zometa for management of locally advanced breast cancer with serum VEGF as primary endpoint: The NEOZOL study
Introduction
Neoadjuvant chemotherapy has become the treatment of choice for locally advanced breast cancer. Zoledronic acid (ZA) is a bisphosphonate initially used in the treatment of bone metastases because of its antibone resorption effect. Antitumor effects of ZA, including the inhibition of cell adhesion to mineralized bone or the antiangiogenic effect, have been demonstrated. However, the clinical significance of these effects remains to be determined.
Materials and Methods
We undertook a multicenter open-label randomized trial to analyze the value of adding ZA to neoadjuvant chemotherapy for TNM clinical stage T2/T3 breast cancer. The primary endpoint was the evolution of serum VEGF.
Results
The data from 24 patients were included in the ZA group and 26 in the control group. The evolution of serum VEGF was slightly in favor of ZA at 5.5 months (â0.7% vs. +7.5%), without reaching statistical significance (P = .52). The secondary endpoints were the breast conservation rate (higher with ZA; 83.3% vs. 65.4%; P = NS), pathologic complete response (no effect), and circulating tumor cells (odds ratio, 0.68 in favor of ZA; 95% confidence interval, 0.02-24.36). No cases of jaw necrosis or severe renal failure were observed in either group.
Conclusion
ZA is an antitumor drug of interest because of its multiple effects on tumor biology. Larger trials with longer follow-up that include additional endpoints such as relapse and survival rates would be of interest
Thyroid function alters during neoadjuvant chemotherapy in breast cancer patients: results from the NEOZOTAC trial (BOOG 2010-01)
The prognostic and predictive value of Tregs and tumor immune subtypes in postmenopausal, hormone receptor-positive breast cancer patients treated with adjuvant endocrine therapy: a Dutch TEAM study analysis
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