PDF(Pubmed)
Abstract：
Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that facilitates the adaptation of cancer cells to hypoxic conditions and may be prognostic of breast cancer recurrence. We evaluated the association of HIF-1α expression with breast cancer recurrence, and its association with timing of breast cancer recurrence.
In this population-based case-control study, we included women diagnosed with stage I-III breast cancer between 1985 and 2001, aged 35-69 years, registered in the Danish Breast Cancer Group. We identified 541 cases of breast cancer recurrence among women with estrogen receptor (ER)-positive disease who were treated with tamoxifen for at least 1 year (ER+ TAM+). We also enrolled 300 breast cancer recurrence cases among women with ER-negative disease, not treated with tamoxifen, who survived at least 1 year (ER-/TAM-). Controls were recurrence-free breast cancer patients at the time of case diagnosis, matched to recurrence cases on ER/TAM status, date of surgery, menopausal status, cancer stage, and county of residence. Expression of HIF-1α was measured by immunohistochemistry on tissue microarrays. We fitted logistic regression models to compute odds ratios (ORs) and 95% confidence intervals (CIs) associating HIF-1α expression with recurrence, and with timing of recurrence.
HIF-1α expression was observed in 23% of cases and 20% of controls in the ER+/TAM+ stratum, and in 47% of cases and 48% of controls in the ER-/TAM- stratum. We observed a near-null association between HIF-1α expression in both ER/TAM groups (ER+/TAM+ OR = 1.21, 95%CI 0.88, 1.67 and ER-/TAM- OR = 0.97, 95%CI 0.68, 1.39). HIF-1α expression was not associated with time to recurrence among women in the ER+/TAM+ stratum, but was associated with early recurrence among women in the ER-/TAM- stratum.
In this study, HIF-1α expression was not associated with breast cancer recurrence overall but may be associated with early recurrence among women diagnosed with ER- breast cancer.
In this population-based case-control study, we included women diagnosed with stage I-III breast cancer between 1985 and 2001, aged 35-69 years, registered in the Danish Breast Cancer Group. We identified 541 cases of breast cancer recurrence among women with estrogen receptor (ER)-positive disease who were treated with tamoxifen for at least 1 year (ER+ TAM+). We also enrolled 300 breast cancer recurrence cases among women with ER-negative disease, not treated with tamoxifen, who survived at least 1 year (ER-/TAM-). Controls were recurrence-free breast cancer patients at the time of case diagnosis, matched to recurrence cases on ER/TAM status, date of surgery, menopausal status, cancer stage, and county of residence. Expression of HIF-1α was measured by immunohistochemistry on tissue microarrays. We fitted logistic regression models to compute odds ratios (ORs) and 95% confidence intervals (CIs) associating HIF-1α expression with recurrence, and with timing of recurrence.
HIF-1α expression was observed in 23% of cases and 20% of controls in the ER+/TAM+ stratum, and in 47% of cases and 48% of controls in the ER-/TAM- stratum. We observed a near-null association between HIF-1α expression in both ER/TAM groups (ER+/TAM+ OR = 1.21, 95%CI 0.88, 1.67 and ER-/TAM- OR = 0.97, 95%CI 0.68, 1.39). HIF-1α expression was not associated with time to recurrence among women in the ER+/TAM+ stratum, but was associated with early recurrence among women in the ER-/TAM- stratum.
In this study, HIF-1α expression was not associated with breast cancer recurrence overall but may be associated with early recurrence among women diagnosed with ER- breast cancer.
摘要：
缺氧诱导因子-1α（HIF-1α）是一种转录因子，可促进癌细胞适应缺氧条件，并可能预测乳腺癌复发。我们评估了HIF-1α表达与乳腺癌复发的关系。及其与乳腺癌复发时间的关系。
在这项基于人群的病例对照研究中，我们纳入了1985年至2001年间诊断为I-III期乳腺癌的女性，年龄在35-69岁之间，在丹麦乳腺癌组织注册。我们在接受他莫昔芬治疗至少1年（ERTAM）的雌激素受体（ER）阳性疾病女性中发现了541例乳腺癌复发。我们还纳入了300例ER阴性女性乳腺癌复发病例，没有用他莫昔芬治疗，存活至少1年（ER-/TAM-）。对照组为病例诊断时的无复发乳腺癌患者，与ER/TAM状态的复发病例相匹配，手术日期,更年期状态，癌症阶段，和居住县。在组织微阵列上通过免疫组织化学测量HIF-1α的表达。我们拟合了逻辑回归模型，以计算将HIF-1α表达与复发相关联的比值比（OR）和95％置信区间（CI）。和复发的时机。
在ER+/TAM+地层中23%的病例和20%的对照中观察到HIF-1α表达,在ER-/TAM-层中，有47％的病例和48％的对照。我们观察到两个ER/TAM组的HIF-1α表达之间几乎为零相关(ER+/TAM+OR=1.21,95CI0.88,1.67和ER-/TAM-OR=0.97,95CI0.68,1.39)。在ER+/TAM+层的女性中,HIF-1α表达与复发时间无关,但与ER-/TAM-层女性的早期复发有关.
在这项研究中,HIF-1α表达与乳腺癌总体复发无关，但可能与诊断为ER-乳腺癌的女性早期复发有关。
在这项基于人群的病例对照研究中，我们纳入了1985年至2001年间诊断为I-III期乳腺癌的女性，年龄在35-69岁之间，在丹麦乳腺癌组织注册。我们在接受他莫昔芬治疗至少1年（ERTAM）的雌激素受体（ER）阳性疾病女性中发现了541例乳腺癌复发。我们还纳入了300例ER阴性女性乳腺癌复发病例，没有用他莫昔芬治疗，存活至少1年（ER-/TAM-）。对照组为病例诊断时的无复发乳腺癌患者，与ER/TAM状态的复发病例相匹配，手术日期,更年期状态，癌症阶段，和居住县。在组织微阵列上通过免疫组织化学测量HIF-1α的表达。我们拟合了逻辑回归模型，以计算将HIF-1α表达与复发相关联的比值比（OR）和95％置信区间（CI）。和复发的时机。
在ER+/TAM+地层中23%的病例和20%的对照中观察到HIF-1α表达,在ER-/TAM-层中，有47％的病例和48％的对照。我们观察到两个ER/TAM组的HIF-1α表达之间几乎为零相关(ER+/TAM+OR=1.21,95CI0.88,1.67和ER-/TAM-OR=0.97,95CI0.68,1.39)。在ER+/TAM+层的女性中,HIF-1α表达与复发时间无关,但与ER-/TAM-层女性的早期复发有关.
在这项研究中,HIF-1α表达与乳腺癌总体复发无关，但可能与诊断为ER-乳腺癌的女性早期复发有关。
