Changes in practice of breast cancer radiotherapy 1998–2002: An Australasian survey

In order to assess the impact on radiation oncology practice of the publication of evidence-based guidelines for technical aspects of therapeutic radiation for breast cancer, the Radiation Oncology Expert Advisory Group of the National Breast Cancer Centre conducted two postal surveys of radiation oncologists practising in Australia and New Zealand. Results from a survey conducted in 1998, prior to distribution of the guidelines, have been published previously. This article reports on results from a survey undertaken in 2002 and contains data from 102 respondents who manage women with breast cancer. The results show several important changes in practice since 1998, including increased use of CT scanning in breast cancer treatment planning and increased use of immobilization devices for patient treatment. There is also evidence of increased attention to technical aspects of treatment planning that reduce the potential risk of treatment toxicity. The influence of the guidelines, the wider availability of modern equipment and results from landmark clinical trials on change in radiation therapy practice is discussed.     

p53 Codon 72 polymorphism predicts the pathologic response to neoadjuvant chemotherapy in patients with breast cancer.

PURPOSE: Recent studies have highlighted that the p53 codon 72 polymorphism plays a crucial role in modulating wild-type p53 apoptotic capacity, and as such may influence the response to chemotherapy. Thus, the purpose of this study was to investigate whether the p53 codon 72 polymorphism might influence pathologic response to neoadjuvant chemotherapy in primary breast cancer. EXPERIMENTAL DESIGN: One hundred and ten operable breast cancer patients received anthracycline-based neoadjuvant chemotherapy and p53 codon 72 polymorphism status was analyzed by PCR-RFLP. RESULTS: The distribution of initial clinical stage, tumor size, estrogen receptor or progesterone receptor status, menopausal status, or erbB2 expression was not significantly different among the polymorphic variants. However, we found that only 13% (3 of 23) of patients with the Pro/Pro variant had a good pathologic response, defined as a complete pathologic response or minimal residual disease. In comparison, 40% (22 of 55) or 37.5% (12 of 32) of patients with the Pro/Arg or Arg/Arg variant had a good pathologic response (P = 0.019). Moreover, patients with the Pro/Pro variant were more likely to have a positive axillary lymph node status than those with the Pro/Arg or Arg/Arg variant (P = 0.007). Furthermore, in multivariate analysis, p53 codon 72 polymorphism was found to be a strong predictor of pathologic response (odds ratio 6.7, 95% confidence interval, 1.4-31.2; P = 0.016). CONCLUSION: Our study indicates that breast cancer patients with the Pro/Pro variant may be less sensitive to anthracycline-based treatment than those with the Pro/Arg or Arg/Arg variant and suggests that analysis of p53 codon 72 polymorphism may provide a simple predictive marker for selecting the right breast cancer patients to anthracycline-based neoadjuvant chemotherapy in clinical setting.     

RECK、MMP 9在三阴性乳腺癌组织芯片中的表达及临床意义

【摘要】 目的 探讨基质金属蛋白酶抑制剂(RECK)、基质金属蛋白酶 9(MMP 9)在三阴性乳腺癌（TNBC）组织、癌旁组织中的表达及与TNBC临床病理的关系。方法 选择绵阳市中心医院乳腺外科2011年5月~2013年7月经病理证实为TNBC的72例石蜡标本及同 患者癌旁组织,利用免疫组化组织芯片技术检测其RECK、MMP 9蛋白的表达。结果 RECK在TNBC组织及癌旁组织中阳性表达率分别为4306%、8056%（P=0000）。TNBC中RECK的表达与临床分期（P=0009）、组织学分级（P=0010）、腋窝淋巴结转移情况（P=0000）相关。MMP 9在TNBC组织及癌旁组织中阳性表达率分别为625%、1528%（P=0000）。TNBC中MMP 9的表达与肿瘤大小（P=0017）、临床分期（P=0001）、组织学分级（P=0001）、腋窝淋巴结转移状况（P=0001）、Ki 67表达情况（P=0034）相关。TNBC中RECK与MMP 9表达呈负相关(r= 0195,P＜005)。结论 RECK的表达缺失与MMP 9过度表达与TNBC浸润、转移有关,有望成为TNBC的预后指标,并且有可能成为TNBC治疗的靶点。     

Overexpression of NIMA-related kinase 6 (NEK6) contributes to malignant growth and dismal prognosis in Human Breast Cancer

NIMA Related Kinase 6 (Nek6) is a protein kinase involved in various cellular processes, including cell cycle regulation, apopotosis, senescence, telomere maintainance and chemoresistance. In the present study, we investigated the role of Nek6 in breast tumorigenesis and the prognostic merit of Nek6 expression in breast cancer. Immunohistochemistry and Western blot analyses was conducted to determine the expression profile of Nek6 in 133 breast cancer specimens. Nek6 was overexpressed in a majority of breast cancer specimens, compared with the adjacent non-tumorous tissues. Furthermore, we revealed that high expression of Nek6 was associated with histologic grade, tumor size and TNM stage in breast cancer. Liner regression analysis showed a significant association between the levels of Nek6 and Ki-67. Cox regression analysis indicated that Nek6 expression was an independent prognostic predictor for breast cancer. Moreover, intracellular level of Nek6 was remarkably increased following the release from serum starvation in MCF-7 cells. EdU incorporation assay indicated that depletion of Nek6 remarkably impaired the proliferation of MCF-7 cells. Finally, spheroid formation assay revealed that interference of Nek6 led to diminished oncospheroid-forming capacity of breast cancer cells. In conclusion, our results imply that Nek6 plays a facilitating role in breast cancer cell proliferation and may serve as a promising therapeutic target for breast cancer.     

Epirubicin and docetaxel with or without capecitabine as neoadjuvant treatment for early breast cancer: final results of a randomized phase III study (ABCSG-24)

BackgroundThis randomized phase III trial compared pathologic complete response (pCR) rates of early breast cancer (EBC) following neoadjuvant epirubicin–docetaxel (ED) ± capecitabine (C), and evaluated the addition of trastuzumab in HER2-positive tumors.Patients and methodsPatients with invasive breast cancer (except T4d) were randomly assigned to receive six 3-weekly cycles of ED (both 75 mg/m²) ± C (1000 mg/m², twice daily, days 1–14). Patients with HER2-positive disease were further randomized to receive trastuzumab (8 mg/kg, then 6 mg/kg every 3 weeks) or not. Primary end point: pCR rate at the time of surgery.ResultsFive hundred thirty-six patients were randomized to ED (n = 266) or EDC (n = 270); 93 patients were further randomized to trastuzumab (n = 44) or not (n = 49). pCR rate was significantly increased with EDC (23.0% versus 15.4% ED, P = 0.027), and nonsignificantly further increased with trastuzumab (38.6% EDC versus 26.5% ED, P = 0.212). Rates of axillary node involvement at surgery and breast conservation were improved with EDC versus ED, but not significantly; the addition of trastuzumab had no further impact. Hormone receptor status, tumor size, grade, and C (all P ≤ 0.035) were independent prognostic factors for pCR. Trastuzumab added to ED ± C significantly increased the number of serious adverse events (35 versus 18; P = 0.020), mainly due to infusion-related reactions.ConclusionThese findings show that the integration of C into a neoadjuvant taxane-/anthracycline-based regimen is a feasible, safe, and effective treatment option, with incorporation of trastuzumab in HER2-positive disease.Clinical trial numberNCT00309556, www.clinicaltrials.gov.     

Pretreatment anti-Müllerian hormone predicts for loss of ovarian function after chemotherapy for early breast cancer

AimImproving survival for women with early breast cancer (eBC) requires greater attention to the consequences of treatment, including risk to ovarian function. We have assessed whether biochemical markers of the ovarian reserve might improve prediction of chemotherapy related amenorrhoea.MethodsWomen (n = 59, mean age 42.6 years [(range 23.3–52.5]) with eBC were recruited before any treatment. Pretreatment ovarian reserve markers (anti-Müllerian hormone [AMH], follicle-stimulating hormone [FSH], inhibin B) were analysed in relation to ovarian status at 2 years.ResultsPretreatment AMH was significantly lower in women with amenorrhoea at 2 years (4.0 ± 0.9 pmol/L versus 17.2 ± 2.5, P < 0.0001), but FSH and inhibin B did not differ between groups. By logistic regression, pretreatment AMH, but not age, FSH or inhibin B, was an independent predictor of ovarian status at 2 years (P = 0.005; odds ratio 0.013). We combined these data with a similar cohort (combined n = 75); receiver–operator characteristic analysis for AMH gave area under curve (AUC) of 0.90 (95% confidence interval (CI) 0.82–0.97)). A cross-validated classification tree analysis resulted in a binary classification schema with sensitivity 98.2% and specificity 80.0% for correct classification of amenorrhoea.ConclusionPretreatment AMH is a useful predictor of long term post chemotherapy loss of ovarian function in women with eBC, adding significantly to the only previously established individualising predictor, i.e. age. AMH measurement may assist decision-making regarding treatment options and fertility preservation procedures.