Effects of ovarian ablation or suppression on breast cancer recurrence and survival: patient-level meta-analysis of 15 000 women in 23 randomised trials.

We assess the effects of OFS on breast cancer outcomes among premenopausal women and how they vary by patient or tumour characteristics and receipt of other treatments.

我们评估了卵巢功能抑制(OFS)对绝经前女性乳腺癌结果的影响，以及这些影响如何根据患者或肿瘤特征以及其他治疗的接受情况而变化。

Methods

We conducted a meta-analysisof individual participant data from the randomised trials comparing OFS versus no OFS, in women with ER-positive or ER-unknown early breast cancer who were premenopausal at randomisation and younger than 55 years.

我们对随机试验的个体参与者数据进行了荟萃分析，比较了卵巢功能抑制（OFS）与不使用OFS，在随机分组时为绝经前且年龄小于55岁的ER阳性或ER未知的早期乳腺癌女性中的效果。

Trials were categorised by whether premenopausal status was or was not confirmed after chemotherapy (if given), and by allocation to tamoxifen.

试验根据化疗后是否确认绝经前状态（如果进行了化疗），以及分配到他莫昔芬的情况进行分类。

Primary outcomes were invasive breast cancer recurrence, breast cancer mortality, other mortality, and all-cause mortality.

主要结果包括侵袭性乳腺癌复发、乳腺癌死亡、其他原因死亡和全因死亡。

ER-weighted log-rank methods estimated event rate ratios (RRs) for ER-positive disease.

ER加权对数秩方法估计了ER阳性疾病的事件率比（RRs）。

Results

Datasets were provided for 23 of 25 identified eligible trials, comprising 18 851 (98·9%) of 19 053 randomly assigned women.

提供了25项已识别的符合条件试验中的23个数据集，包括18 851名（占19 053名随机分配女性的98.9%）女性。

Among 15 075 premenopausal women with ER-positive or ER-unknown tumours, allocation to OFS significantly reduced recurrence rates (RR 0·82, 95% CI 0·77-0·87; p<0·00001), with larger reductions in women who were confirmed premenopausal after chemotherapy (or who did not receive chemotherapy) than in those with unconfirmed premenopausal status after chemotherapy; heterogeneity p=0·0004.

在15 075名绝经前的女性中，对ER阳性或ER未知的肿瘤进行卵巢功能抑制（OFS）显著降低了复发率（RR 0.82，95% CI 0.77-0.87；p<0.00001），在经过化疗后确认为绝经前状态的女性中复发率的降低幅度大于化疗后绝经前状态未确认的女性；异质性p=0.0004。

Among confirmed premenopausal women, recurrence reductions were larger in older trials without tamoxifen (RR 0·61, 0·52-0·71; p<0·0001) than in more recent trials of OFS plus tamoxifen versus tamoxifen (RR 0·79, 0·70-0·91; p=0·0008).

在已确认的绝经前妇女中，未使用他莫昔芬的早期试验中复发率降低幅度较大（相对风险 RR 0·61, 95% 置信区间 CI 0·52-0·71; p<0·0001），与近期试验中卵巢功能抑制（OFS）联合他莫昔芬与单用他莫昔芬相比的复发率降低幅度（RR 0·79, 95% CI 0·70-0·91; p=0·0008）相比。

In these more recent trials, the additional recurrence reduction with OFS appeared larger in women younger than 45 years than in women aged 45-54 years (RR 0·73, 0·63-0·86 vs RR 0·95, 0·75-1·21; p=0·072); in those younger than 45 years, breast cancer mortality was similarly improved (RR 0·74, 0·58-0·94; p=0·012).

在这些较新的试验中，对于年龄小于45岁的女性，卵巢功能抑制（OFS）带来的额外复发率降低似乎比45至54岁的女性更大（RR 0·73, 95% CI 0·63-0·86 vs RR 0·95, 95% CI 0·75-1·21; p=0·072）；在45岁以下的女性中，乳腺癌死亡率也有所改善（RR 0·74, 95% CI 0·58-0·94; p=0·012）。

There was no increase in deaths without recurrence.

无复发生存的死亡人数没有增加。

Findings did not differ significantly by OFS method or other recorded patient or tumour characteristics.

通过卵巢功能抑制（OFS）方法或其他记录的患者或肿瘤特征，研究结果没有显著差异。

interpretation

For premenopausal women with ER-positive early breast cancer, even if chemotherapy or tamoxifen are given, OFS significantly reduces the 15-year risk of recurrence and death.

对于绝经前的ER阳性早期乳腺癌女性，即使接受了化疗或他莫昔芬治疗，卵巢功能抑制（OFS）显著降低了15年复发和死亡风险。

funding

Nuffield Department of Population Health, University of Oxford; Cancer Research UK; the Breast Cancer Research Foundation; and the UK Medical Research Council.

牛津大学Nuffield人口健康系；癌症研究英国；乳腺癌研究基金会；以及英国医学研究委员会。