Mammographic density as an image-based biomarker of therapy response in neoadjuvant-treated breast cancer patients

Abstract

Purpose Personalized cancer treatment requires predictive biomarkers, including image-based biomarkers. Breast cancer (BC) patients receiving neoadjuvant chemotherapy (NACT) are in a clinically vulnerable situation with the tumor present. This study investigated whether mammographic density (MD), assessed pre-NACT, is predictive of pathological complete response (pCR). Methods A total of 495 BC patients receiving NACT in Sweden 2005–2019 were included, merged from two different cohorts. Cohort 1 was retrospectively collected (n = 295) and cohort 2 was prospectively collected (n = 200). Mammograms were scored for MD pre-NACT according to the Breast Imaging-Reporting and Data System (BI-RADS), 5th Edition. The association between MD and accomplishing pCR post-NACT was analyzed using logistic regression models—for the whole cohort, stratified by menopausal status, and in different St. Gallen surrogate subtypes. Results In comparison to patients with low MD (BI-RADS a), the multivariable-adjusted odds ratio (OR) of accomplishing pCR following NACT was on a descending scale: 0.62 (95% confidence interval (CI) 0.24–1.57), 0.38 (95% CI 0.14–1.02), and 0.32 (95% CI 0.09–1.08) for BI-RADS b, c, and d, respectively. For premenopausal patients selectively, the corresponding point estimates were lower, although wider CIs: 0.31 (95% CI 0.06–1.62), 0.24 (95% CI 0.04–1.27), and 0.13 (95% CI 0.02–0.88). Subgroup analyses based on BC subtypes resulted in imprecise estimates, i.e., wide CIs. Conclusions It seemed as though patients with higher MD at baseline were less likely to reach pCR after NACT—a finding more pronounced in premenopausal women. Larger multicenter studies are needed to enable analyses and interpretation for different BC subtypes.

The association between breast density and breast cancer pathological response to neoadjuvant chemotherapy

“…Previously, the same group performed a retrospective study of 302 patients and concluded that women with BI-RADS d MD were less likely to achieve pCR post-NACT after adjusting for age and pre-treatment tumour characteristics. The results of both study sets were recently collated [ 14 ] and demonstrated that pre-menopausal women with category MD d were less likely to achieve pCR after NACT [ 14 ]. Conversely, a recent study of 442 patients by Di Cosimo et al concluded that those with denser breasts showed an increased likelihood of pCR with odds ratio (OR) of 1.70, 2.79 and 1.47 for b , c and d categories.…”

Changes in Automated Mammographic Breast Density Can Predict Pathological Response After Neoadjuvant Chemotherapy in Breast Cancer

“…Recently, Swedish researchers analyzed the association between pCR after NCT and MD using visual assessment with BI-RADS in 495 patients with breast cancer [ 12 ]. In a model adjusted for patient age, BMI, and menopausal status, the pCR rates were significantly lower in premenopausal women classified as BI-RADS D, which represents extremely dense breasts [ 12 ].…”

“…Recently, Swedish researchers analyzed the association between pCR after NCT and MD using visual assessment with BI-RADS in 495 patients with breast cancer [ 12 ]. In a model adjusted for patient age, BMI, and menopausal status, the pCR rates were significantly lower in premenopausal women classified as BI-RADS D, which represents extremely dense breasts [ 12 ]. Consistently, our multivariable analysis confirmed that higher Qabd categories and decreased ΔVbd% were significantly independently associated with lower pCR rates, whereas aggressive breast cancer subtype, high-grade tumor, and use of anti-HER2 agents with chemotherapy were significantly associated with increased pCR rates after NCT.…”

“…Previous studies have suggested that NCT or adjuvant chemotherapy could reduce MD, probably as a secondary effect of chemotherapy-induced amenorrhea [ 10 11 ]. Regarding the predictive role of MD scored according to the Breast Imaging-Reporting and Data System (BI-RADS) in patients who underwent NCT, a recent report associated a higher MD at pre-NCT that was visually assessed by an experienced specialist in radiology with failure to achieve pCR, with this relationship being more pronounced in premenopausal patients with breast cancer [ 12 ]. In clinical practice, mammography is performed twice, before and after the completion of NCT, to evaluate response, and changes in MD also need to be considered.…”

Analysis of mammograms using artificial intelligence to predict response to neoadjuvant chemotherapy in breast cancer patients: proof of concept

“…1. The study cohort (453 patients) consisted of a retrospective (N = 258, treatment period 2005-2016) and a prospective cohort (N = 195, treatment period 2014-2019) as previously described [18]. The inclusion criteria for both cohorts were female patients treated with NACT undergoing the intended breast surgery.…”