Mammographic density parameters and breast cancer tumor characteristics among postmenopausal women

Abstract

Purpose

Mammographic density is an important breast cancer risk factor, although it is not clear whether the association differs across breast cancer tumor subtypes. We examined the association between indicators of mammographic density and breast cancer risk by tumor subtype among postmenopausal women by investigating heterogeneity across tumor characteristics.

Methods

Mammographic density measures were determined for 477 breast cancer cases and 588 controls, all postmenopausal, in Vancouver, British Columbia, using digitized screening mammograms and Cumulus software. Mammographic dense (DA), non-dense (NDA), and percent dense (PDA) areas were treated as continuous covariates and categorized into quartiles according to the distribution in controls. For cases only, tests for heterogeneity between tumor subtypes were assessed by multinomial logistic regression. Associations between mammographic density and breast cancer risk were modeled for each subtype separately through unconditional logistic regression.

Results

Heterogeneity was apparent for the association of PDA with tumor size (p-heterogeneity=0.04). Risk did not differ across the other assessed tumor characteristics (p-heterogeneity values >0.05).

Conclusion

These findings do not provide strong evidence that mammographic density parameters differentially affect specific breast cancer tumor characteristics.

Keywords:

• mammographic density
• breast cancer
• tumor characteristics
• heterogeneity
• multinomial logistic regression

Acknowledgments

We thank Drs. Gertraud Maskarinec, Jennifer Stone, and Martin Yaffe for their kind assistance to ascertain our mammographic density readings’ consistency. We would like to express our deep gratitude to Ms. Karen Locken and Mrs. Christine Lam (BC Cancer Agency, Diagnostic Images), as well as the staff of the Screening Mammography Program of British Columbia, particularly Mrs. Carla Brown–John for their invaluable help. We highly appreciate the extensive support provided by Ms. Anoma Gunasekara, Mr. Gord Mawdsley (Sunnybrook Research Institute), Mrs. Zenaida Abanto (BC Cancer, Cancer Control Research), and the staff of the BC Cancer Registry, Breast Cancer Outcomes Unit.

Funding for the original study was provided by a grant from the Canadian Institutes of Health Research (PI: KJA, Funding Reference #69036). HAVG was supported by a Four Year Doctoral Fellowship Award from the University of British Columbia, and a Canadian Breast Cancer Foundation Fellowship (award #319404).

Abbreviations

aOR, adjusted odds ratio; BC, British Columbia; BMI, body mass index; CBCS, Canadian Breast Cancer Study; DA, mammographic dense area; DAG, directed acyclic graph; ER, estrogen receptor; FISH, fluorescence in situ hybridization; HER2, human epidermal factor receptor 2; HRT, hormone replacement therapy; IHC, immunohistochemistry; NDA, mammographic non-dense area; PDA, mammographic percent dense area; PR, progesterone receptor.

Ethics approval and informed consent

Ethical approval for this study was provided by the University of British Columbia, British Columbia Cancer Agency Research Ethics Board (reference #H14-01614).

Data availability

The analyzed datasets are available from the corresponding author on reasonable request.

Disclosure

The authors report no conflicts of interest in this work.