Epidemiologic risk factors for in situ and invasive ductal breast cancer among regularly screened postmenopausal women by grade in the Cancer Prevention Study-II Nutrition Cohort

  • Samantha PuvanesarajahEmail author
  • Susan M. Gapstur
  • Ted Gansler
  • Mark E. Sherman
  • Alpa V. Patel
  • Mia M. Gaudet
Original Paper



Histopathologic grade provides an integrated measure of biologic features which affects cancer prognosis. In invasive ductal breast cancer (IDBC), the grade of the ductal carcinoma in situ (DCIS) and invasive components are usually concordant, suggesting grade is established early in tumorigenesis and may be linked to etiologic factors. In this study, we used prospectively collected data from postmenopausal women in the Cancer Prevention Study-II (CPS-II) Nutrition Cohort to compare risk factor associations among low-grade and high-grade DCIS, as well as low-grade and high-grade IDBC.


Among 73,825 cancer-free women at enrollment in the CPS-II Nutrition Cohort in 1992–1993 (mean age: 62.1 years), we verified 802 diagnosed with DCIS (C50 8500/2; n = 430 low-grade and 372 high-grade) and 3,125 with IDBC (C50 8500/3; n = 2,221 low-grade and 904 high-grade) through June 2013. Person-time contribution was conditional on screening mammograms self-reported on biennial surveys. Multivariable-adjusted joint Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI).


A personal history of benign breast disease was more strongly associated with higher risk of low-grade DCIS (HR = 2.20, 95% CI 1.81–2.67; p for heterogeneity = 0.0004) than high-grade DCIS. Consumption of two or more alcoholic drinks/day was only associated with a higher risk of low-grade IDBC (HR = 1.58, 95% CI 1.33–1.88; p for heterogeneity = 0.005).


These results suggest heterogeneity by grade for breast cancer etiology. Identification of potential risk factor differences among low-grade and high-grade DCIS and IDBC may help to clarify associations, and ultimately, improve breast cancer risk prediction models.


Epidemiology Etiology DCIS Invasive breast cancer 



The authors express sincere appreciation to all Cancer Prevention Study participants, and to each member of the study and biospecimen management group. The authors would like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention's National Program of Cancer Registries and cancer registries supported by the National Cancer Institute's Surveillance Epidemiology and End Results Program.


The views expressed here are those of the authors and do not necessarily represent the American Cancer Society or the American Cancer Society—Cancer Action Network.


Dr. Puvanesarajah was supported by the American Cancer Society’s Cancer Prevention Studies Post-Doctoral Fellowship Program. The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II cohort.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All aspects of the CPS-II Nutrition Cohort have been reviewed and approved by the Emory University Institutional Review Board.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

10552_2019_1253_MOESM1_ESM.docx (37 kb)
Supplementary file1 (DOCX 49 kb)


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Behavioral and Epidemiology Research GroupAmerican Cancer SocietyAtlantaUSA
  2. 2.Department of Health Sciences ResearchMayo ClinicJacksonvilleUSA

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