Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
School of Population Health, Royal College of Surgeons in Ireland, Dublin, Ireland.
JNCI Cancer Spectr. 2022 May 2;6(3). doi: 10.1093/jncics/pkac028.
Mammographic breast density (MBD) decline post-tamoxifen initiation is a favorable prognostic factor in estrogen receptor (ER)-positive breast cancer (BC) and has potential utility as a biomarker of tamoxifen response. However, the prognostic value of MBD decline may vary by molecular characteristics among ER-positive patients.
We investigated associations between MBD decline (≥10% vs <10%) and breast cancer-specific mortality (BCSM) among ER-positive breast cancer patients aged 36-87 years at diagnosis treated with tamoxifen at Kaiser Permanente Northwest (1990-2008). Patients who died of BC (case patients; n = 62) were compared with those who did not (control patients; n = 215) overall and by tumor molecular characteristics (immunohistochemistry [IHC]-based subtype [luminal A-like: ER-positive/progesterone receptor [PR]-positive/HER2-negative/low Ki67; luminal B-like: ER-positive and 1 or more of PR-negative, HER2-positive, high Ki67] and modified IHC [mIHC]-based recurrence score of ER/PR/Ki67). Percent MBD was measured in the unaffected breast at baseline mammogram (mean = 6 months before tamoxifen initiation) and follow-up (mean = 12 months post-tamoxifen initiation). Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed from logistic regression models. All statistical tests were 2-sided.
MBD decline was statistically significantly associated with reduced risk of BCSM overall (OR = 0.38, 95% CI = 0.15 to 0.92). This association was, however, stronger among women with aggressive tumor characteristics including luminal B-like (OR = 0.17, 95% CI = 0.04 to 0.73) vs A-like (OR = 0.74, 95% CI = 0.19 to 2.92); large (OR = 0.26, 95% CI = 0.08 to 0.78) vs small (OR = 0.41, 95% CI = 0.04 to 3.79) tumors; PR-negative (OR = 0.02, 95% CI = 0.001 to 0.37) vs PR-positive (OR = 0.50, 95% CI = 0.18 to 1.40) disease; and high (OR = 0.25, 95% CI = 0.07 to 0.93) vs low (OR = 0.44, 95% CI = 0.10 to 2.09) mIHC3 score.
The findings support MBD decline as a prognostic marker of tamoxifen response among patients with aggressive ER-positive BC phenotypes, for whom understanding treatment effectiveness is critical.
在雌激素受体（ER）阳性乳腺癌（BC）患者中，他莫昔芬治疗后乳腺密度（MBD）下降是一个有利的预后因素，并且作为他莫昔芬反应的生物标志物具有潜在的效用。然而，MBD 下降的预后价值可能因 ER 阳性患者的分子特征而异。
我们研究了诊断时年龄为 36-87 岁的接受他莫昔芬治疗的 ER 阳性乳腺癌患者中，MBD 下降（≥10%比<10%）与乳腺癌特异性死亡率（BCSM）之间的关联。与未死亡的 BC 患者（对照患者；n=215）相比，死于 BC 的患者（病例患者；n=62）进行了总体比较，并根据肿瘤分子特征（免疫组化[IHC] 为基础的亚型[ER 阳性/孕激素受体[PR]-阳性/HER2-阴性/低 Ki67；luminal B-like：ER 阳性和 1 个或多个 PR-阴性、HER2 阳性、高 Ki67]和改良 IHC[mIHC]-基于 ER/PR/Ki67 的复发评分）进行了比较。在基线乳房 X 线照片（他莫昔芬起始前平均=6 个月）和随访（他莫昔芬起始后平均=12 个月）时测量未受影响乳房的 MBD 百分比。使用逻辑回归模型计算调整后的优势比（OR）和 95%置信区间（CI）。所有统计检验均为双侧。
MBD 下降与 BCSM 风险降低具有统计学显著相关性（OR=0.38，95%CI=0.15 至 0.92）。然而，在具有侵袭性肿瘤特征的女性中，这种关联更强，包括 luminal B-like（OR=0.17，95%CI=0.04 至 0.73）与 A-like（OR=0.74，95%CI=0.19 至 2.92）；大（OR=0.26，95%CI=0.08 至 0.78）与小（OR=0.41，95%CI=0.04 至 3.79）肿瘤；PR 阴性（OR=0.02，95%CI=0.001 至 0.37）与 PR 阳性（OR=0.50，95%CI=0.18 至 1.40）疾病；和高（OR=0.25，95%CI=0.07 至 0.93）与低（OR=0.44，95%CI=0.10 至 2.09）mIHC3 评分。
这些发现支持 MBD 下降作为 ER 阳性侵袭性 BC 表型患者中他莫昔芬反应的预后标志物，对于了解治疗效果至关重要。
