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乳腺钼靶筛查结果为阴性后 年轻乳腺癌女性的预后较差 编者按：大约有15%的患者在上次接受乳腺钼靶筛查结果为阴性之后、下次例行筛查之前被诊断出乳腺癌。这些间隔癌（两次筛查间隔期被诊断出的癌症病例）既包括乳腺钼靶筛查间隔期发生的癌症，也包括筛查遗漏的癌症和快速生长的癌症，这些癌症的症状明显，并且与筛查时发现的癌症相比，预后往往较差。定期乳腺钼靶筛查除了可以确定乳腺癌风险高并且预后较差的女性，针对这些乳腺钼靶筛查可能不够的女性还可以进行补充筛查。 2018年5月3日，《美国医学会杂志》肿瘤学分册在线发表哈佛大学医学院及其教学医院（麻省总医院、布列根女子医院）、西雅图癌症研究生物统计学研究所、宾夕法尼亚大学佩雷尔曼医学院、西雅图弗雷德哈钦森癌症研究中心、佛蒙特大学癌症中心的人群研究个体化方案优化筛查（PROSPR）协作组大数据分析，对乳腺钼靶筛查结果为阴性后被诊断出乳腺癌患者预后不良的发生率和风险因素进行了评定。 该大数据分析的乳腺钼靶数据来自PROSPR协作组，研究人群包括2011～2014年接受乳腺钼靶筛查、既往未被诊断出乳腺癌的年龄≥40岁女性共30万6028例，其最初的乳腺钼靶结果阴性，乳腺影像报告数据系统（BI-RADS）分类为1或2（乳腺钼靶属于其他分类均为结果阳性）。根据州癌症登记数据库，确定乳腺钼靶筛查后1年内被诊断出乳腺癌。 预后不良乳腺癌被定义为符合以下任何标准的病例：远处转移；区域淋巴结阳性；雌激素受体阳性和/或孕激素受体阳性和HER2阴性浸润癌直径≥2cm；雌激素受体阴性、孕激素受体阴性、HER2阴性（三阴性）浸润癌直径≥1cm；HER2阳性浸润癌直径≥1cm。该定义为正在进行的分层合成乳腺钼靶筛查研究（TMIST）主要结局。 通过多变量逻辑回归，对年龄、乳腺钼靶密度、家族史与癌症诊断的相关性进行评定。通过SAS软件9.4版进行所有分析，P值≤0.05被认为具有统计学意义，并且所有P值都是双侧。 结果发现，乳腺钼靶筛查结果为阴性后被诊断出乳腺癌的病例，与乳腺钼靶筛查结果为阳性后被诊断出乳腺癌的病例相比，预后不良比例较高（43.8%比26.9%）。 对于所有乳腺钼靶结果为阴性的女性：
相反，对于所有乳腺钼靶筛查结果为阳性的女性：
因此，该大数据分析结果表明，乳腺钼靶筛查结果的阳性预测值取决于患者年龄和家族史，但是与乳腺钼靶密度无关。相反，阴性预测值取决于乳腺钼靶密度，但是与患者年龄或家族史无关。虽然乳腺钼靶筛查结果为阴性后被诊断为乳腺癌的发生率很低，但是该情况与预后不良相关的可能性，提醒我们需要加强这些女性的早期发现。虽然乳腺钼靶密度总体上可以预测间隔癌，但是对于该间期癌是否预后不良的预测能力较弱。年龄较小可以预测间隔癌预后不良，这可能反映了间隔癌的双重来源。可能存在但是通过乳腺钼靶筛查未检出的乳腺癌可能与老年女性预后良好相关，而筛查间隔癌可能与年轻女性乳腺癌快速生长且预后不良相关。该研究的局限性在于仅少数患者特征可用，限制了被评定的风险因素数量。 总之，乳腺钼靶密度作为公认是否需要进行补充筛查的主要因素，受到了广泛的关注，但是同时考虑年龄，可能更有效确定有预后不良乳腺癌风险的女性。 相关阅读 JAMA Oncol. 2018 May 3. [Epub ahead of print] Breast Cancer With a Poor Prognosis Diagnosed After Screening Mammography With Negative Results. Anne Marie McCarthy; William E. Barlow; Emily F. Conant; Jennifer S. Haas; Christopher I. Li; Brian L. Sprague; Katrina Armstrong; PROSPR Consortium. Massachusetts General Hospital, Harvard Medical School, Boston; Cancer Research and Biostatistics, Seattle, Washington; University of Pennsylvania Perelman School of Medicine, Philadelphia; Brigham and Women's Hospital, Boston, Massachusetts; Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Vermont Cancer Center, University of Vermont, Burlington. This study of data from the PROSPR consortium assesses the incidence of and risk factors associated with breast cancer with a poor prognosis after undergoing screening mammography with negative results. Approximately 15% of breast cancers are diagnosed after the patient undergoes screening mammography with negative results and before the next recommended screening examination. These interval cancers (cases of cancer diagnosed during the interval between examinations) include both cancers that were present during screening mammography but were missed on examination and rapidly growing cancers that present symptomatically and tend to have a poorer prognosis than cancers detected during screening. Identifying women who are at high risk of breast cancer with a poor prognosis despite regular screening mammography could enable targeted supplemental screening for women for whom screening mammography may not be sufficient. This study describes the incidence of and risk factors associated with breast cancer with a poor prognosis after screening mammography with negative findings. METHODS: Mammography data were obtained from the Population-Based Research Optimizing Screening Through Personalized Regimens (PROSPR) consortium, which includes Dartmouth Hitchcock Medical Center (Lebanon, New Hampshire), Brigham and Women's Hospital (Boston, Massachusetts), University of Pennsylvania Health System (Philadelphia), and Vermont Breast Cancer Surveillance System (Burlington). The institutional review boards of Dartmouth Hitchcock Medical Center, Brigham and Women's Hospital, the University of Pennsylvania Health System, and the University of Vermont approved the study and waived the need for informed consent. The study population included women 40 years or older with no earlier diagnosis of breast cancer who received screening mammography between 2011 and 2014. Mammograms with negative results were those with an initial Breast Imaging Reporting and Data System category 1 or 2; mammograms in all other categories were classified as having positive results. Cancer diagnoses within 1 year after screening mammography were obtained from state cancer registries. Breast cancer cases with a poor prognosis were defined as cases of cancer meeting any of the following criteria: distant metastases; cancer-positive regional lymph nodes; estrogen receptor-positive and/or progesterone receptor-positive and HER2-negative invasive cancer 2 cm or more in diameter; estrogen receptor-negative, progesterone receptor-negative, HER2-negative (triple-negative) invasive cancer 1 cm or more in diameter; or HER2-positive invasive cancer 1 cm or more in diameter. This definition is the primary outcome for the ongoing Tomosynthesis Mammographic Imaging Screening Trial. Multivariable logistic regression was used to assess the association of age, breast density, and family history with cancer diagnosis. SAS software, version 9.4 (SAS Institute Inc) was used for all analyses. P≤.05 was considered statistically significant, and all P values were 2-sided. RESULTS: Table 1 provides the incidence of breast cancer among 306028 women 40 years or older who had no earlier diagnosis of breast cancer and underwent mammography screening between 2011 and 2014. Cases of cancer diagnosed after screening mammography with negative results were more likely to be associated with a poor prognosis (43.8%) than those diagnosed after mammography with positive results (26.9%). Among all women with negative mammography results (Table 2, Model 1), women with dense breasts had twice the odds of receiving a cancer diagnosis (irrespective of prognosis) compared with women with nondense breasts (odds ratio [OR], 2.07; 95% CI, 1.48-2.89; P=.02). Age and family history were not significantly associated with breast cancer diagnosis after negative screening mammography results. However, among women who received a diagnosis of cancer after negative mammography results (Table 2, Model 2), younger age was associated with having cancer with a poor prognosis (patients aged 40-49 years vs those 70-89 years: OR, 3.52; 95% CI, 1.15-10.72; P=.048; P for trend=.005). Breast density and family history were not significantly associated with poor prognosis. In contrast, for women with positive screening mammogram results, breast density was not associated with any cancer diagnosis, but age (eg, patients aged 40-49 years vs those 70-89 years: OR, 0.22; 95% CI, 0.18-0.26; P<.001) and family history (positive vs negative family history: OR, 1.29; 95% CI, 1.12-1.48; P<.001) were (Table 2, Model 3), and none of these factors were associated with breast cancer with a poor prognosis (Table 2, Model 4). DISCUSSION: Our results indicate that the positive predictive value of mammography results depends on patient age and family history but not on breast density. In contrast, the negative predictive value depends on breast density but not on patient age or family history. Although the rate of breast cancer after negative mammography results is small, the likelihood that such cases will be associated with a poor prognosis highlights the need to improve early detection for these women. Although breast density is predictive of interval cancer overall, it is less predictive of whether that interval cancer will have a poor prognosis. Younger age is predictive of interval breast cancer with a poor prognosis. This may reflect the dual origins of interval cancers. Cancers that are present but not detected by screening mammography may be more likely to be associated with a good prognosis and occur among older women, whereas cancers that develop between screening examinations may be more likely to be rapidly growing cancers associated with a poor prognosis and occur among younger women. Only a few patient characteristics were available, limiting the number of risk factors that were assessed. Breast density has received much attention as the primary factor identifying a need for supplemental screening, but considering both breast density and age may be more effective in identifying women who are at risk for breast cancer with a poor prognosis. DOI: 10.1001/jamaoncol.2018.0352 |
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