Long-term prognostic implications of risk factors associated with tumor size: a case study of women regularly attending screening

Abstract

BackgroundBreast cancer prognosis is strongly associated with tumor size at diagnosis. We aimed to identify factors associated with diagnosis of large (> 2 cm) compared to small tumors, and to examine implications for long-term prognosis.MethodsWe examined 2012 women with invasive breast cancer, of whom 1466 had screen-detected and 546 interval cancers that were incident between 2001 and 2008 in a population-based screening cohort, and followed them to 31 December 2015. Body mass index (BMI) was ascertained after diagnosis at the time of study enrollment during 2009. PD was measured based on the contralateral mammogram within 3 years before diagnosis. We used multiple logistic regression modeling to examine the association between tumor size and body mass index (BMI), mammographic percent density (PD), or hormonal and genetic risk factors. Associations between the identified risk factors and, in turn, the outcomes of local recurrence, distant metastases, and death (153 events in total) in women with breast cancer were examined using Cox regression. Analyses were carried out according to mode of detection.ResultsBMI and PD were the only factors associated with tumor size at diagnosis. For BMI (≥25 vs. < 25 kg/m2), the multiple adjusted odds ratios (OR) were 1.37 (95% CI 1.02–1.83) and 2.12 (95% CI 1.41–3.18), for screen-detected and interval cancers, respectively. For PD (≥20 vs. < 20%), the corresponding ORs were 1.72 (95% CI 1.29–2.30) and 0.60 (95% CI 0.40–0.90). Among women with interval cancers, those with high BMI had worse prognosis than women with low BMI (hazard ratio 1.70; 95% CI 1.04–2.77), but PD was not associated with the hazard rate. Among screen-detected cancers, neither BMI nor PD was associated with the hazard rate.ConclusionsIn conclusion, high BMI was associated with the risk of having a tumor larger than 2 cm at diagnosis. Among women with interval cancer, high BMI was associated with worse prognosis. We believe that women with high BMI should be especially encouraged to attend screening.Electronic supplementary materialThe online version of this article (10.1186/s13058-018-0962-6) contains supplementary material, which is available to authorized users.

Mammography features for early markers of aggressive breast cancer subtypes and tumor characteristics: A population‐based cohort study

“…Consistent with our earlier studies using mammographic density measured on a general numeric/categorical scale, 16,17 we found significant associations of mammographic density measured using clinically relevant cBIRADS with tumor size and detection mode in our study. This is a finding largely explained by the masking effect, whereby high mammographic density reduces mammographic sensitivity, leading to delayed diagnoses and possibly more advanced tumors 32 …”

“…A total of 5715 women (61%) consented to participate—they provided blood, answered detailed questionnaire on lifestyle including hormonal and reproductive factors and consented to retrieval of mammography images. Detailed information on the cohort has been published previously 14‐19 . From these 5715 women, 1169 were excluded for the following reasons; one woman was excluded due to missing diagnosis date, 653 women had noninvasive breast cancer or missing invasiveness, and 515 women had multiple (including contralateral) breast cancer.…”

“…Furthermore, while earlier studies have found that mammographic density could be associated with aggressive breast cancer subtypes and tumor characteristics including interval breast cancer, 14‐19 it remains unclear of the utility of mammographic density when measured in the clinical context using the computer‐generated Breast Imaging Reporting and Data System (cBIRADS) 20 . In addition, emerging studies are showing that women who do not experience physiological mammographic density reduction with age might have an increased risk of breast cancer 21‐23 .…”

“…Detailed information on the cohort has been published previously. [14][15][16][17][18][19] From these 5715 women, 1169 were excluded for the following reasons; one woman was excluded due to missing diagnosis date, 653 women had noninvasive breast cancer or missing invasiveness, and 515 women had multiple (including contralateral) breast cancer. This left 4546 women in our study.…”

Localized mammographic density is associated with interval cancer and large breast cancer: a nested case-control study

“…Cancer size is known to be a strong predictor of breast cancer survival [17]. We confirmed findings in prior studies that large cancers are more often diagnosed in women with high overall density [28, 29]. Our most striking finding was a very strong association between localized density and large cancer, independent of the overall density (Table 4).…”