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Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms.

Publication ,  Journal Article
Kravchenko, J; Akushevich, I; Seewaldt, VL; Abernethy, AP; Lyerly, HK
Published in: Breast Cancer Res Treat
July 2011

The observed bimodal patterns of breast cancer incidence in the U.S. suggested that breast cancer may be viewed as more than one biological entity. We studied the factors potentially contributing to this phenomenon, specifically focusing on how disease heterogeneity could be linked to breast carcinogenesis mechanisms. Using empirical analyses and population-based biologically motivated modeling, age-specific patterns of incidence of ductal and lobular breast carcinomas from the SEER registry (1990-2003) were analyzed for heterogeneity and characteristics of carcinogenesis, stratified by race, stage, grade, and estrogen (ER)/progesterone (PR) receptor status. The heterogeneity of breast carcinoma age patterns decreased after stratification by grade, especially for grade I and III tumors. Stratification by ER/PR status further reduced the heterogeneity, especially for ER(+)/PR(-) and ER(-)/(-) tumors; however, the residual heterogeneity was still observed. The number of rate-limiting events of carcinogenesis and the latency of ductal and lobular carcinomas differed, decreasing from grade I to III, with poorly differentiated tumors associated with the least number of carcinogenesis stages and the shortest latency. Tumor grades play important role in bimodal incidence of breast carcinoma and have distinct mechanisms of carcinogenesis. Race and cancer subtype could play modifying role. ER/PR status contributes to the observed heterogeneity, but is subdominant to tumor grade. Further studies on sources of "remaining" heterogeneity of population with breast cancer (such as genetic/epigenetic characteristics) are necessary. The results of this study could suggest stratification rather than unification of breast cancer prevention strategies, risk assessment, and treatment.

Duke Scholars

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Published In

Breast Cancer Res Treat

DOI

EISSN

1573-7217

Publication Date

July 2011

Volume

128

Issue

2

Start / End Page

483 / 493

Location

Netherlands

Related Subject Headings

  • SEER Program
  • Risk Factors
  • Receptors, Progesterone
  • Receptors, Estrogen
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Racial Groups
  • Prognosis
  • Oncology & Carcinogenesis
  • North Carolina
 

Citation

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Kravchenko, J., Akushevich, I., Seewaldt, V. L., Abernethy, A. P., & Lyerly, H. K. (2011). Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms. Breast Cancer Res Treat, 128(2), 483–493. https://doi.org/10.1007/s10549-011-1347-z
Kravchenko, Julia, Igor Akushevich, Victoria L. Seewaldt, Amy P. Abernethy, and H Kim Lyerly. “Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms.Breast Cancer Res Treat 128, no. 2 (July 2011): 483–93. https://doi.org/10.1007/s10549-011-1347-z.
Kravchenko J, Akushevich I, Seewaldt VL, Abernethy AP, Lyerly HK. Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms. Breast Cancer Res Treat. 2011 Jul;128(2):483–93.
Kravchenko, Julia, et al. “Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms.Breast Cancer Res Treat, vol. 128, no. 2, July 2011, pp. 483–93. Pubmed, doi:10.1007/s10549-011-1347-z.
Kravchenko J, Akushevich I, Seewaldt VL, Abernethy AP, Lyerly HK. Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms. Breast Cancer Res Treat. 2011 Jul;128(2):483–493.
Journal cover image

Published In

Breast Cancer Res Treat

DOI

EISSN

1573-7217

Publication Date

July 2011

Volume

128

Issue

2

Start / End Page

483 / 493

Location

Netherlands

Related Subject Headings

  • SEER Program
  • Risk Factors
  • Receptors, Progesterone
  • Receptors, Estrogen
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Racial Groups
  • Prognosis
  • Oncology & Carcinogenesis
  • North Carolina