【原】乳腺钼靶筛查结果假阳性仍须警惕

　　通过乳腺钼靶筛查早期发现乳腺癌进行早期治疗，可将乳腺癌死亡率降低20%以上，故已被瑞典等高福利国家普及。不过，乳腺钼靶筛查结果假阳性率也较高，美国大约为11%，欧洲大约为2.5%。目前，乳腺钼靶筛查结果假阳性后乳腺癌发生率和死亡率等长期结局尚不明确。

　　2023年11月2日，《美国医学会杂志》肿瘤学分册在线发表瑞典卡罗林斯卡学院、斯德哥尔摩南方医院、中国浙江大学和福建医科大学的大数据分析报告，调查了乳腺钼靶筛查结果假阳性后长期结局，并调查了乳腺钼靶筛查结果假阳性与癌症的关联是否受到基线特征、肿瘤特征和假结果阳性后时间长短的影响。

　　该全国人群匹配队列研究于1991年1月1日～2020年3月31日在瑞典进行，其中包括1991～2017年乳腺钼靶筛查结果首次假阳性的4万5213例女性，以及年龄、乳腺钼靶筛查日历年份和筛查史匹配、既往无假阳性结果的45万2130例对照者。该研究还包括有乳腺钼靶测得乳腺密度数据的1113例结果假阳性女性和1万1130例匹配对照者，这些数据来自卡罗林斯卡乳腺钼靶筛查项目乳腺癌风险预测研究。统计学分析于2022年4月～2023年2月进行。主要结局衡量指标为乳腺癌的发生率和死亡率。

　　结果，该研究队列共计49万7343例女性（年龄中位52岁，四分位42～59岁）。

　　有假阳性结果与无假阳性结果的女性相比，20年乳腺癌累积发生率为11.3%比7.3%（95%置信区间：10.7%～11.9%、7.2%～7.5%），对年龄、乳腺钼靶筛查日历年份、乳腺癌家族史、学历等影响因素进行校正后，乳腺癌发生风险高61%（风险比：1.61，95%置信区间：1.54～1.68）。

　　筛查时年龄为60～75岁女性乳腺癌发生风险高102%（风险比：2.02，95%置信区间：1.80～2.26），乳腺钼靶筛查乳腺密度较低女性乳腺癌发生风险高365%（风险比：4.65，95%置信区间：2.61～8.29））。

　　召回复查时接受活检与未接受活检的女性相比，乳腺癌发生风险更高（风险比：1.77比1.51，95%置信区间：1.63～1.92、1.43～1.60）。

　　结果假阳性后同侧乳腺癌发生风险高于对侧乳腺癌（风险比：1.92比1.28，95%置信区间：1.81～2.04、1.20～1.37），并且随访前4年乳腺癌发生风险较高（前2年、2～4年、6～10年、10～20年风险比：2.57、1.93、1.69、1.51，95%置信区间：2.33～2.85、1.76～2.12、1.57～1.82、1.33～1.72）。

　　不同肿瘤特征对乳腺癌发生风险的影响未见统计学差异，除了肿瘤大小≥20毫米与<20毫米相比乳腺癌发生风险显著较高（风险比：1.78比1.47，95%置信区间：1.64～1.93、1.38～1.56）。

　　此外，有假阳性结果与无假阳性结果的女性相比，全因死亡风险相似，乳腺癌所致死亡风险高84%（风险比：1.84，95%置信区间：1.57～2.15）。

　　因此，该研究结果表明，乳腺钼靶筛查结果假阳性后发生乳腺癌的风险因个体特征和随访情况而异，这些结果有助于出现假阳性结果后进行个体化的乳腺癌风险筛查。对于乳腺钼靶筛查结果假阳性的女性，应该强调对乳腺癌的长期重视，制定个体化监测计划可能对这些女性有益。

JAMA Oncol. 2023 Nov 2. IF: 28.4

Breast Cancer Incidence After a False-Positive Mammography Result.

Mao X, He W, Humphreys K, Eriksson M, Holowko N, Yang H, Tapia J, Hall P, Czene K.

Karolinska Institutet, Stockholm, Sweden; Zhejiang University, Hangzhou, Zhejiang, China; Fujian Medical University, Fuzhou, China; Sodersjukhuset, Stockholm, Sweden.

This Swedish cohort study examines long-term outcomes after a false-positive mammography result and investigates whether the association of a false-positive mammography result with cancer differs by baseline characteristics, tumor characteristics, and time since the false-positive result.

QUESTION: What are the long-term outcomes for women who receive a false-positive mammography result?

FINDINGS: In this population-based, matched cohort study in Sweden, women with a false-positive mammography result had an elevated incidence of breast cancer and mortality for up to 20 years; the increased breast cancer risk varied according to age, mammographic breast density, and whether a biopsy was performed during recall or not. In addition, the risk of breast cancer was more pronounced during the initial years after the false-positive mammography result.

MEANING: This study suggests that breast cancer awareness should be emphasized long term for women with a false-positive mammography result; developing personalized surveillance programs can be beneficial for these women.

IMPORTANCE: False-positive mammography results are common. However, long-term outcomes after a false-positive result remain unclear.

OBJECTIVES: To examine long-term outcomes after a false-positive mammography result and to investigate whether the association of a false-positive mammography result with cancer differs by baseline characteristics, tumor characteristics, and time since the false-positive result.

DESIGN, SETTING, AND PARTICIPANTS: This population-based, matched cohort study was conducted in Sweden from January 1, 1991, to March 31, 2020. It included 45213 women who received a first false-positive mammography result between 1991 and 2017 and 452130 controls matched on age, calendar year of mammography, and screening history (no previous false-positive result). The study also included 1113 women with a false-positive result and 11 130 matched controls with information on mammographic breast density from the Karolinska Mammography Project for Risk Prediction of Breast Cancer study. Statistical analysis was performed from April 2022 to February 2023.

EXPOSURE: A false-positive mammography result.

MAIN OUTCOMES AND MEASURES: Breast cancer incidence and mortality.

RESULTS: The study cohort included 497343 women (median age, 52 years [IQR, 42-59 years]). The 20-year cumulative incidence of breast cancer was 11.3% (95% CI, 10.7%-11.9%) among women with a false-positive result vs 7.3% (95% CI, 7.2%-7.5%) among those without, with an adjusted hazard ratio (HR) of 1.61 (95% CI, 1.54-1.68). The corresponding HRs were higher among women aged 60 to 75 years at the examination (HR, 2.02; 95% CI, 1.80-2.26) and those with lower mammographic breast density (HR, 4.65; 95% CI, 2.61-8.29). In addition, breast cancer risk was higher for women who underwent a biopsy at the recall (HR, 1.77; 95% CI, 1.63-1.92) than for those without a biopsy (HR, 1.51; 95% CI, 1.43-1.60). Cancers after a false-positive result were more likely to be detected on the ipsilateral side of the false-positive result (HR, 1.92; 95% CI, 1.81-2.04) and were more common during the first 4 years of follow-up (HR, 2.57; 95% CI, 2.33-2.85 during the first 2 years; HR, 1.93; 95% CI, 1.76-2.12 at >2 to 4 years). No statistical difference was found for different tumor characteristics (except for larger tumor size). Furthermore, associated with the increased risk of breast cancer, women with a false-positive result had an 84% higher rate of breast cancer death than those without (HR, 1.84; 95% CI, 1.57-2.15).

CONCLUSIONS AND RELEVANCE: This study suggests that the risk of developing breast cancer after a false-positive mammography result differs by individual characteristics and follow-up. These findings can be used to develop individualized risk-based breast cancer screening after a false-positive result.

PMID: 37917078

DOI: 10.1001/jamaoncol.2023.4519