尽管丰胸度下降与他莫昔芬治疗相关，并伴有更大的治疗效益，但有限的数据表明内分泌症状也可能与改善乳腺癌结局有关。但是，目前尚不清楚内分泌症状是否与他莫昔芬开始治疗后乳腺密度减少相关。在一项为期12个月的纵向研究中，我们评估了74名女性在处方他莫昔芬后的治疗相关内分泌症状和乳腺密度变化。通过创新的全乳腺超声断层成像（m/s）评估治疗相关内分泌症状和乳腺密度声速测量，分别在他莫昔芬治疗前（T0）和开始治疗后1-3个月（T1）、4-6个月（T2）和12个月（T3）进行测量。CYP2D6基因型和他莫昔芬代谢物在T3时被测量。使用多元线性回归，根据年龄、种族、绝经状态、体重指数和基线密度调整，估计了治疗相关内分泌症状对乳腺密度变化的平均影响。观察到有显著内分泌症状的女性乳腺密度下降明显（T1的平均变化（95%置信区间）为-0.26 m/s（-2.17,1.65）；T2为-2.12 m/s（-4.02,-0.22）；T3为-3.73 m/s（-5.82,-1.63）；p趋势=0.004），但这种情况在没有症状的女性中并未观察到（p趋势=0.18）（p交互作用=0.02）。在症状频率增加时，也观察到了类似的下降趋势（无症状p趋势=0.91；低/中度症状p趋势=0.03；高症状p趋势=0.004）。在具有可检测的他莫昔芬代谢物或中等/高效CYP2D6代谢者状态的女性中，密度下降仍然存在。患有突发/恶化内分泌症状的女性在开始接受他莫昔芬治疗后，其乳腺密度会出现明显下降。需要进一步研究以评估这些观察结果是否预测临床结果。如果证实，内分泌症状可能是他莫昔芬响应的代理和诊断工具，有助于患者和医生加强依从性。 © 2023. 这是美国政府的作品，未受到美国的版权保护；但可能适用于其他国家的版权保护。

Although breast density decline with tamoxifen therapy is associated with greater therapeutic benefit, limited data suggest that endocrine symptoms may also be associated with improved breast cancer outcomes. However, it is unknown whether endocrine symptoms are associated with reductions in breast density after tamoxifen initiation. We evaluated treatment-associated endocrine symptoms and breast density change among 74 women prescribed tamoxifen in a 12-month longitudinal study. Treatment-associated endocrine symptoms and sound speed measures of breast density, assessed via novel whole breast ultrasound tomography (m/s), were ascertained before tamoxifen (T0) and at 1-3 (T1), 4-6 (T2), and 12 months (T3) after initiation. CYP2D6 status was genotyped, and tamoxifen metabolites were measured at T3. Using multivariable linear regression, we estimated mean change in breast density by treatment-associated endocrine symptoms adjusting for age, race, menopausal status, body mass index, and baseline density. Significant breast density declines were observed in women with treatment-associated endocrine symptoms (mean change (95% confidence interval) at T1:-0.26 m/s (-2.17,1.65); T2:-2.12 m/s (-4.02,-0.22); T3:-3.73 m/s (-5.82,-1.63); p-trend = 0.004), but not among women without symptoms (p-trend = 0.18) (p-interaction = 0.02). Similar declines were observed with increasing symptom frequency (p-trends for no symptoms = 0.91; low/moderate symptoms = 0.03; high symptoms = 0.004). Density declines remained among women with detectable tamoxifen metabolites or intermediate/efficient CYP2D6 metabolizer status. Emergent/worsening endocrine symptoms are associated with significant, early declines in breast density after tamoxifen initiation. Further studies are needed to assess whether these observations predict clinical outcomes. If confirmed, endocrine symptoms may be a proxy for tamoxifen response and useful for patients and providers to encourage adherence.© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.