Can Neoadjuvant Chemotherapy Reduce Breast Density?
Neoadjuvant chemotherapy (NAT) is commonly used before surgery in women with triple-negative and HER2-positive breast cancers.
Multiple studies have established that tamoxifen therapy consistently reduces mammographic breast density [1], serving as a powerful predictor of clinical benefit. Research demonstrates that women experiencing at least a 10% decrease in density had a 63% reduction in primary breast cancer risk [2], while those with pronounced reductions saw a 50% to 56% lower risk of breast cancer-specific mortality [3,4], a 55% lower risk of a contralateral primary [5] and a significantly reduced risk of recurrence [4,6]. While breast density is known to be influenced by hormonal factors, less is known about how chemotherapy affects mammographic density or whether density changes correlate with treatment
response.
In a new retrospective study [7], investigators in Italy evaluated paired pre- and post-treatment mammograms from 135 women with stage T1-2N0M0 triple-negative and/or HER2-positive invasive ductal breast cancer treated with NAT between 2018 and 2023. Mammograms included digital mammography and digital breast tomosynthesis obtained before and after treatment. The authors assessed changes in BI-RADS breast density based on an expert reader (and validated by in-house AI software) and examined whether density reduction was associated with pathological response to therapy.
Key findings:
- Breast density decreased significantly after NAT, with the proportion of women classified as having dense breasts (BI-RADS C or D) falling from 46.7% before treatment to 24.4% after treatment. a
- Women with greater reductions in breast density were more likely to have a favorable pathological response to chemotherapy. b
- The greatest reductions in density were seen in younger, premenopausal women and in women who had the densest breasts before treatment.
- An AI tool demonstrated good agreement with an expert breast radiologist in assessing density changes and performed more consistently than less experienced readers. c
Reduced density after treatment may improve visualization of residual or recurrent disease on mammography and may facilitate surgical planning. These findings suggest that mammographic density may be a dynamic imaging feature that reflects treatment-related changes in breast tissue. Although density reduction cannot yet be considered a validated biomarker of treatment response, the results support further investigation into whether changes in density could provide additional information about the effectiveness of NAT.
a Dense breast categories (BI-RADS C/D) decreased from 46.7% (63/135) before NAT to 24.4% (33/135) after NAT (P<0.001). BI-RADS C (heterogeneously dense) decreased from 31.9% (43/135) to 17.8% (24/135), while BI-RADS D (extremely dense) decreased from 14.8% (20/135) to 6.7% (9/135).
b Greater density reduction was associated with a better pathological response to chemotherapy (Spearman rho = 0.53). Younger age (OR 0.74) and premenopausal status (OR 1.89) were independent predictors of larger density reductions.
c Agreement between the AI tool and the expert breast radiologist was good (ICC = 0.78) and exceeded agreement with a moderately experienced radiologist (ICC = 0.68), a radiology resident (ICC = 0.55), and a non-radiologist reader (ICC = 0.39).
References
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2. Cuzick J, Warwick J, Pinney E, et al. Tamoxifen-induced reduction in mammographic density and breast cancer risk reduction: a nested case-control study. J Natl Cancer Inst. 2011;103(9):744- 752. doi:10.1093/jnci/djr079.
3. Li J, Humphreys K, Eriksson L, Edgren G, Czene K, Hall P. Mammographic density reduction is a prognostic marker of response to adjuvant tamoxifen therapy in postmenopausal patients with breast cancer. J Clin Oncol. 2013;31(18):2249-2256. doi:10.1200/JCO.2012.44.5015.
4. Shawky MS, Martin H, Hugo HJ, et al. Mammographic density: a potential monitoring biomarker for adjuvant and preventative breast cancer endocrine therapies. Oncotarget. 2017;8(3):5578-5591.
5. Sandberg MEC, Li J, Hall P, et al. Change of mammographic density predicts the risk of contralateral breast cancer: a case-control study. Breast Cancer Res. 2013;15(4):R57. doi:10.1186/bcr3451.
6. Kim JY, Cho N, Jeyanth JX, et al. Smaller reduction in 3D breast density associated with subsequent cancer recurrence in patients with breast cancer receiving adjuvant tamoxifen therapy. AJR Am J Roentgenol. 2014;202(4):912-921. doi:10.2214/AJR.13.11109.
7. Pesapane F, Sorce A, Di Millo B, et al. Impact of neoadjuvant chemotherapy on breast tissue density and its correlation with pathologic response: a retrospective AI-enhanced radiological study. Br J Radiol. 2026;99. doi:10.1093/bjr/tqag114.