New insights into breast microcalcification for poor prognosis: NACT cohort and bone metastasis evaluation cohort

The study aimed to analyze the poor prognosis of microcalcification in breast cancer (BC), including the pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) and the risk of bone metastases.

313 breast cancer patients received NACT to evaluate pCR and 1182 patients from a multicenter database to assess bone metastases were retrospectively included. Two groups were divided according to the presence or absence of mammography microcalcification. Clinical data, image characteristics, neoadjuvant treatment response, bone involvement, and follow-up information were recorded. The pCR and bone metastases were compared between subgroups using the Mann-Whitney and χ² tests and logistic regression, respectively.

Mammographic microcalcification was associated with a lower pCR than uncalcified BC in the NACT cohort (20.6% vs 31.6%, P = 0.029). Univariate and multivariate analysis suggested that calcification was a risk factor for poor NACT response [OR = 1.780, 95%CI (1.065-2.974), P = 0.028], [OR = 2.352, 95%CI (1.186-4.667), P = 0.014]. Microcalcification was more likely to be necrosis on MRI than those without microcalcification (53.0% vs 31.7%, P < 0.001), multivariate analysis indicated that tumor necrosis was also a risk factor for poor NACT response [OR = 2.325, 95%CI (1.100-4.911), P = 0.027]. Age, menopausal status, breast density, mass, molecular, and pathology type were not significantly associated with non-pCR risk assessment. In a multicenter cohort of 1182 patients with pathologically confirmed BC, those with microcalcifications had a higher proportion of bone metastases compared to non-calcified BC (11.6% vs 4.9%, P < 0.001). Univariate and multivariate analysis showed that microcalcification was an independent risk factor for bone metastasis [OR = 2.550, 95%CI (1.620-4.012), P < 0.001], [OR = 2.268(1.263-4.071), P = 0.006)]. Osteolytic bone metastases predominated but there was no statistical difference between the two groups (78.9% vs 60.7%, P = 0.099). Calcified BC was mainly involved in axial bone, but was more likely to involve the whole-body bone than non-calcified BC (33.8% vs 10.7%, P = 0.021).

This study provides important insights into the poor prognosis of microcalcification, not only in terms of poor response to NACT but also the risk factor of bone metastases.