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Purpose Mammographic Density (MD) refers to the amount of fibroglandular breast tissue present in the breast and is an established risk factor for developing breast cancer. The ability to evaluate treatment response dynamically renders neoadjuvant chemotherapy (NACT) the preferred treatment option in many clinical scenarios. Previous studies have suggested that MD can predict patients likely to achieve a pathological complete response (pCR) to NACT. We aimed to determine whether there is a causal relationship between BI-RADS breast composition categories for breast density at diagnosis and the pCR rate and residual cancer burden score (RCB) by performing a retrospective review on consecutive breast cancer patients who received NACT in a tertiary referral centre from 2015 to 2021. Methods The Mann–Whitney U Test was used to test for differences between two independent groups (i.e. those who achieved pCR and those who did not). A binary logistic regression model was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI) for an association between the independent variables of molecular subtype, MD, histological grade and FNA positivity and the dependant variable of pCR. Statistical analysis was conducted with SPSS (IBM SPSS for Mac, Version 26.0; IBM Corp). Results 292 patients were included in the current study. There were 124, 155 and 13 patients in the BI-RADS MD category b, c and d, respectively. There were no patients in the BI-RADS MD category a. The patients with less dense breast composition (MD category b) were significantly older than patients with denser breast composition (MD category c, d) (p = 0.001) and patients who had a denser breast composition (MD category d) were more likely to have ER+ tumours. There was no significant difference in PgR status, HER2 status, pathological complete response (pCR), FNA positivity, or RCB class dependent upon the three MD categories. A binary logistic regression revealed that patients with HER2-enriched breast cancer and triple-negative breast cancer are more likely to achieve pCR with an OR of 3.630 (95% CI 1.360–9.691, p = 0.010) and 2.445 (95% CI 1.131–5.288, p = 0.023), respectively. Conclusion Whilst dense MD was associated with ER positivity and these women were less likely to achieve a pCR, MD did not appear to independently predict pCR post-NACT.

Background The Clinical Treatment Score post-5 years (CTS5) integrates four clinicopathological variables to estimate the residual disease recurrence risk in hormone receptor-positive breast cancer patients who have been treated with five years of adjuvant endocrine therapy. This study aimed to determine the accuracy of the CTS5. Methods A systematic review was performed in accordance with the PRISMA statement. Studies relevant for inclusion in the current review were identified from The Cochrane Library, EBSCO, Ovid, PubMed, and Embase. Results Six papers reported on 30 354 postmenopausal patients (age range 42 to 91 years). The pooled hazard ratio (HR) of distant recurrence relative to the low-risk CTS5 category was 5.41 (95% c.i. 4.50 to 6.51; P < 0.05) for the high-risk CTS5 category and 2.32 (95% c.i. 1.90–2.84; P < 0.05) for the intermediate CTS5 category. Three papers reported on 10 425 premenopausal patients (age range 18 to 54 years). The pooled HR of distant recurrence relative to the low-risk CTS5 category was 5.42 (95% c.i. 2.26 to 13.01; P < 0.05) for the high-risk CTS5 category and 2.82 (95% c.i. 1.35 to 5.88; P < 0.05) for the intermediate CTS5 category. Relative to high-risk postmenopausal patients, the mean observed 10-year distant recurrence risk for the high CTS5 category was 13.83 per cent, which differs significantly from the CTS5 estimation of 10-year distant recurrence risk (20.3 per cent, 95% c.i. 17.2 to 24; P = 0.000). Conclusion The CTS5 can predict late distant recurrence risk in pre- and postmenopausal hormone receptor-positive breast cancer patients. CTS5 overestimates the risk for high-risk patients and thus, its use in these patients warrants caution.

Background. While hormone receptor-positive (HR+), HER 2-negative (HER2-), node-negative breast cancer is associated with an excellent overall prognosis, it possesses a unique penchant for late recurrence. Estimating breast cancer recurrence has traditionally relied on clinicopathologic markers, such as those underpinning the Clinical Treatment Score Post 5 years (CTS5) but there is an increasing dependence on multigene molecular signatures such as the Oncotype DX 21-gene recurrence score (ODX-RS). The purpose of this current study was to examine the relationship between the novel CTS5 and the ODX-RS with an observational cohort study. Methods. The CTS5 and ODX-RS were calculated for 1,358 patients who were diagnosed with HR+, HER2-VE, node-negative, invasive breast cancer. The cohort was split according to menopausal status as defined by age. 381 pre-menopausal (<52 years) and 977 post-menopausal (≥ 52 years) patients were included in the analysis. Correlation statistics were used to investigate the relationship between the CTS5 and the ODX-RS. Results. Considering the CTS5 and ODX-RS as categorical and continuous variables respectively, there was a significant relationship between the CST5 and the ODX-RS categories (Pearson's chi-squared (x2) p <0.001), and a high ODX-RS was weakly associated with a high CTS5 RS (Pearson product moment correlation pre-menopausal r=0.274, p<0.05; post-menopausal r=0.222, p<0.05). Conclusion. The current study demonstrates a weak but statistically significant correlation between the CTS5 and the ODX-RS that is independent of age. This finding mirrors previous research which indicates that the ODX-RS is poorly correlated with traditional clinicopathologic features used to predict recurrence risk.

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