Согласно исследованию, опубликованному в Nature Communications, рак молочной железы, выявленный между скрининговыми маммограммами, с большой степенью вероятности может сочетаться с другими видами рака как до, так и после постановки его диагноза.
Исследователи изучили истории болезни почти 15 000 женщин с диагнозом рак молочной железы из двух когорт, Swedish cohorts и Women's Health Initiative. Около 12% случаев рака были интервальными, то есть были диагностированы в период между отрицательной и следующей запланированной маммографиями. У женщин с интервальным раком молочной железы значительно чаще, чем у женщин с раком, обнаруженным при скрининге, были диагностированы иные опухоли до постановки диагноза рака молочной железы, а также и после постановки диагноза рака молочной железы. Кроме того, женщины с интервальным раком чаще имели онкологические заболевания в анамнезе опухоли. Результаты данных исследований должны учитываться при выработке программ скрининга и профилактики различных видов рака у женщин.
- Felix Grassmann et al
Breast cancer (BC) patients diagnosed between two screenings (interval cancers) are more likely than screen-detected patients to carry rare deleterious mutations in cancer genes potentially leading to increased risk for other non-breast cancer (non-BC) tumors. In this study, we include 14,846 women diagnosed with BC of which 1,772 are interval and 13,074 screen-detected. Compared to women with screen-detected cancers, interval breast cancer patients are more likely to have a non-BC tumor before (Odds ratio (OR): 1.43 [1.19–1.70], P = 9.4 x 10−5) and after (OR: 1.28 [1.14–1.44], P = 4.70 x 10−5) breast cancer diagnosis, are more likely to report a family history of non-BC tumors and have a lower genetic risk score based on common variants for non-BC tumors. In conclusion, interval breast cancer is associated with other tumors and common cancer variants are unlikely to be responsible for this association. These findings could have implications for future screening and prevention programs.
Breast cancer screenings reduces breast cancer mortality by up to 35%1,2. However, in women regularly attending screening, between 20 and 30% of breast cancers are not detected by screening mammography but are diagnosed between screening intervals3. Failure of mammographic-screening protocols to detect cancer can be attributed to many different factors ranging from technical (e.g., imaging technology and radiologist interpretation)4 to patient specific (e.g., age, co-morbidities, and breast/mammographic density)5 to biological (e.g., the aggressive tumor grows to pathological, and palpable size within the screening window).
Compared with breast cancers detected at a screening, interval cancers are characterized by more-aggressive tumor characteristics and poorer prognosis (i.e., increased mortality) in most recent studies (summarized in ref. 6). Patients with interval breast cancer usually present with an average higher histological grade7,8, larger tumor size9, and more-metastatic local lymphnodes10, a higher proportion of estrogen receptor (ER)8/progesterone receptor (PR) negativity11, a higher frequency of HER2 positivity8,9, and are more often triple negative12.
Currently, few risk factors for interval breast cancers are known. Apart from high mammographic density13 and current hormone replacement therapy (HRT)12,14 use, a previous false-positive mammographic screening15 as well as family history of breast cancer within first degree family members14,15,16 have been implicated in interval cancer risk. Recently, we have shown that interval cancer cases (compared with screen-detected cancers) have a lower breast cancer genetic risk score (GRS), i.e., carry fewer breast cancer risk increasing alleles17. Conversely, rare loss of function mutations in 31 known and suspected breast cancer predisposition genes were found to be more common in interval cancer cases than in screen-detected cases18.
Loss of function mutations in those genes are also frequently found to predispose individuals for other types of cancer19 and may increase the incidence of other tumors in those individuals or in close relatives. In this study, we find that interval cancer patients are more likely than screen-detected patients to be diagnosed with other tumors, either before or after breast cancer diagnosis and that rather rare and not common variants are responsible for the observed the association. Our results thus reveal insights into risk and consequence of interval breast cancer.
Investigating socio-economic and reproductive risk factors for interval cancer
The current study included 14,846 breast cancer patients (1,772 interval cancer patients and 13,074 screen-detected cancer patients) from three cohorts (Table 1). Among known breast cancer risk factors, we found that interval compared with screen-detected breast cancer patients are more likely to have given birth before 25 years of age (OR: 1.13, 95% CI: 1.00–1.27, PLR < 0.05, logistic regression, Wald test), are less likely to have a college degree (OR: 0.85, 95% CI: 0.77–0.96, PLR < 0.01) and are more likely to report the use of hormone replacement therapy (OR: 1.29, 95% CI: 1.15–1.45, PLR < 0.001) as well as a family history of breast cancer in close relatives (OR: 1.14, 95% CI: 1.01–1.29, PLR < 0.05, Table 1). Importantly, interval cancers were consistently more likely than screen-detected cancers to have worse tumor characteristics and prognosis across the three cohorts (Table 1 and Supplementary Fig. 1).