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Background: Mammographic density (MD) is an established predictor of risk of a first breast cancer, but the relationship of MD to contralateral breast cancer (CBC) risk is not clear, including the roles of age, mammogram timing, and change with treatment. Multivariable prediction models for CBC risk are needed and MD could contribute to these., Methods: We conducted a case-control study of MD and CBC risk in phase II of the WECARE study where cases had a CBC diagnosed ≥ 2 years after first diagnosis at age <55 years and controls had unilateral breast cancer (UBC) with similar follow-up time. We retrieved film mammograms of the unaffected breast from two time points, prior to/at the time of the first diagnosis (253 CBC cases, 269 UBC controls) and ≥ 6 months up to 48 months following the first diagnosis (333 CBC cases, 377 UBC controls). Mammograms were digitized and percent MD (%MD) was measured using the thresholding program Cumulus. Odds ratios (OR) and 95% confidence intervals (CI) for association between %MD and CBC, adjusted for age, treatment, and other factors related to CBC, were estimated using logistic regression. Linear regression was used to estimate the association between treatment modality and change in %MD in 467 women with mammograms at both time points., Results: For %MD assessed following diagnosis, there was a statistically significant trend of increasing CBC with increasing %MD (p = 0.03). Lower density (<25%) was associated with reduced risk of CBC compared to 25 to < 50% density (OR 0.69, 95% CI 0.49, 0.98). Similar, but weaker, associations were noted for %MD measurements prior to/at diagnosis. The relationship appeared strongest in women aged < 45 years and non-existent in women aged 50 to 54 years. A decrease of ≥ 10% in %MD between first and second mammogram was associated marginally with reduced risk of CBC (OR 0.63, 95% CI 0.40, 1.01) compared to change of <10%. Both tamoxifen and chemotherapy were associated with statistically significant 3% decreases in %MD (p < 0.01)., Conclusions: Post-diagnosis measures of %MD may be useful to include in CBC risk prediction models with consideration of age at diagnosis. Chemotherapy is associated with reductions in %MD, similar to tamoxifen.

Background: Timely coordinated diagnostic assessment following an abnormal screening mammogram reduces patient anxiety and may optimise breast cancer prognosis. Since 1998, the Ontario Breast Screening Program (OBSP) has offered organised assessment through Breast Assessment Centres (BACs). For OBSP women seen at a BAC, an abnormal mammogram is followed by coordinated referrals through the use of navigators for further imaging, biopsy, and surgical consultation as indicated. For OBSP women seen through usual care (UC), further diagnostic imaging is arranged directly from the screening centre and/or through their physician; results must be communicated to the physician who is then responsible for arranging any necessary biopsy and/or surgical consultation. This study aims to evaluate factors associated with diagnostic wait times for women undergoing assessment through BAC and UC., Methods: Of the 2 147 257 women aged 50-69 years screened in the OBSP between 1 January 2002 and 31 December 2009, 155 866 (7.3%) had an abnormal mammogram. A retrospective design identified two concurrent cohorts of women diagnosed with screen-detected breast cancer at a BAC (n=4217; 47%) and UC (n=4827; 53%). Multivariable logistic regression analyses examined associations between wait times and assessment and prognostic characteristics by pathway. A two-sided 5% significance level was used., Results: Screened women with breast cancer were two times more likely to be diagnosed within 7 weeks when assessed through a BAC vs UC (OR=1.91, 95% CI=1.73-2.10). In addition, compared with UC, women assessed through a BAC were significantly more likely to have their first assessment procedure within 3 weeks of their abnormal mammogram (OR=1.25, 95% CI=1.12-1.39), ⩽3 assessment procedures (OR=1.54, 95% CI=1.41-1.69), ⩽2 assessment visits (OR=1.86, 95% CI=1.70-2.05), and ⩾2 procedures per visit (OR=1.41, 95% CI=1.28-1.55). Women diagnosed through a BAC were also more likely than those in UC to have imaging (OR=1.99, 95% CI=1.44-2.75) or a biopsy (OR=3.69, 95% CI=2.64-5.15) vs consultation only at their first assessment visit, and two times more likely to have a core or FNA biopsy than a surgical biopsy (OR=2.08, 95% CI=1.81-2.40). Having ⩽2 assessment visits was more likely to reduce time to diagnosis for women assessed through a BAC compared with UC (BAC OR=10.58, 95% CI=8.96-12.50; UC OR=4.47, 95% CI=3.94-5.07), as was having ⩽3 assessment procedures (BAC OR=4.97, 95% CI=4.26-5.79; UC OR=2.95, 95% CI=2.61-3.33). Income quintile affected wait times only in women diagnosed in UC, with those in the two highest quintiles more likely to receive a diagnosis in 7 weeks., Conclusions: Women with screen-detected breast cancer in OBSP were more likely to have shorter wait times if they were diagnosed through organised assessment. This might be as a result of women diagnosed through a BAC having more procedures per visit, procedures scheduled in shorter intervals, and imaging or biopsy on their first visit. Given the significant improvement in timeliness to diagnosis, women with abnormal mammograms should be managed through organised assessment.

Purpose: Variations during breast tissue development can influence later breast cancer risk. In particular, prolonged nulliparity increases risk. The authors used optical spectroscopy to compare breast tissue in 115 nulliparous women aged 31-40 (group 2) to 140 nulliparous women aged 18-21 (group 1), and also to 36 parous women aged 31-40 (group 3), and to evaluate the relationship between IGF-1 and optical breast tissue properties. IGF-1 has been linked in particular to premenopausal breast cancer., Methods: The authors measured the transmission spectra from 625 to 1050 nm wavelengths in each breast and determined regions of interindividual variation using principal components analysis. Spectral differences represent variation in lipid, water, oxyhemoglobin, deoxyhemoglobin, and collagen content. Group differences and the relationship with IGF-1 were estimated by linear regression after adjustment for multiple factors including height, weight, ethnicity, hormonal contraceptive use, and days since last menstrual period., Results: Principal component 3 scores were more negative in the older nulliparous women compared to either younger nulliparous women or to parous women of the same age (beta = -0.16, p = 0.008 for group 2 vs group 1 and beta = 0.51, p = 0.03 for group 3 vs group 2). These differences appear to indicate increased deoxyhemoglobin relative to oxyhemoglobin content in the tissue of the older, nulliparous premenopausal women compared to the other groups, which may be an indicator of proportionally increased proliferative tissue. Principal component 4 also differed between older and younger nulliparous women (beta = 0.08, p = 0.02 for group 2 vs. group 1) and was negatively associated with IGF-1 in younger women (beta = -0.0004, p = 0.03) and positively associated with IGF-1 in older women (beta = 0.001, p = 0.004)., Conclusions: Optical spectroscopy may be useful to identify breast tissue at increased risk of cancer development and track changes over time, particularly in young women where exposure to radiation is of particular concern. Additional work is needed to confirm the observed breast tissue differences and to determine the specific tissue chromophore changes with age and parity.