Longitudinal fluctuation in mammographic percent density differentiates between interval and screen-detected breast cancer.
Interval breast cancer (IC) has a more aggressive phenotype and higher mortality than screen-detected cancer (SDC). In this case-case study, we investigated whether the size of longitudinal fluctuations in mammographic percent density (PD fluctuation) was associated with the ratio of IC versus SDC among screened women with breast cancer. The primary study population consisted of 1,414 postmenopausal breast cancer cases, and the validation population of 1,241 cases. We calculated PD fluctuation as the quadratic mean of deviations between actual PD and the long-term trend estimated by a mixed effects model. In a logistic regression model we examined the association between PD fluctuation and IC versus SDC including adjustments for PD at last screening, age at diagnosis, BMI and hormone replacement therapy. All statistical tests were two-sided. There were 385 IC and 1,029 SDC in the primary study population, with PD fluctuations of 0.44 and 0.41 respectively (p = 0.0309). After adjustments, PD fluctuation was associated with an increased ratio of IC versus SDC, with an estimated per-standard deviation odds ratio of 1.17 (95% CI = 1.03-1.33), compared to 1.19 (95% CI = 1.04-1.38) in the validation population. In screened women with breast cancer, high fluctuation in mammographic percent density was associated with an increased ratio of IC versus SDC. Whether this is entirely related to a reduced mammographic detectability or to a biological phenotype promoting faster tumor growth remains to be elucidated.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Department of Diagnostic Radiology, Karolinska University Hospital, Stockholm, Sweden.
Fredrik
http://orcid.org/0000-0003-3910-7086
F
Strand
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Swedish eScience Research Centre (SeRC), Karolinska Institutet, Stockholm, Sweden.
Keith
K
Humphreys
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Mikael
M
Eriksson
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Genome Institute of Singapore, Singapore, Singapore.
Jingmei
J
Li
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Therese M L
TM
Andersson
Department of Cancer Screening, Stockholm-Gotland Regional Cancer Centre, Stockholm, Sweden.
Sven
S
Törnberg
Department of Diagnostic Radiology, Karolinska University Hospital, Stockholm, Sweden.|Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
Edward
E
Azavedo
Department of Radiology and Biomedical Imaging, UCSF School of Medicine, University of California, San Francisco, CA.
John
J
Shepherd
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Per
P
Hall
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Kamila
K
Czene
D000368:Aged; D015992:Body Mass Index; D000071060:Breast Density; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D055088:Early Detection of Cancer; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D016015:Logistic Models; D008327:Mammography / Q000379:methods*; D008875:Middle Aged; D016017:Odds Ratio; D017698:Postmenopause
breast cancer; cancer screening; early detection; interval cancer; longitudinal study; mammographic density; mammography