High mammographic breast density predicts locoregional recurrence after modified radical mastectomy for invasive breast cancer: a case-control study

Abstract

Background: We aimed to evaluate the influence of mammographic breast density at diagnosis on the risk of cancer recurrence and survival outcomes in patients with invasive breast cancer after modified radical mastectomy.

Methods: This case-control study included 121 case-control pairs of women diagnosed with invasive breast cancer between 2004 and 2009, and who had undergone modified radical mastectomy and had mammographic breast density measured before or at diagnosis. Women with known locoregional recurrence or distant metastasis were matched by pathological disease stage, age, and year of diagnosis to women without recurrence. Locoregional recurrence was defined as recurrence in the ipsilateral chest wall, or axillary, internal mammary, or supraclavicular nodes. The median follow-up duration was 84.0 months for case patients and 92.9 months for control patients.

Results: Patients with heterogeneously dense (50-75% density) and extremely dense (>75% density) breasts had an increased risk of locoregional recurrence (hazard ratios 3.1 and 5.7, 95% confidence intervals 1.1-9.8 and 1.2-34.9, p = 0.043 and 0.048, respectively) than did women with less dense breasts. Positive margins after surgery also increased the risk of locoregional recurrence (hazard ratio 3.3, 95% confidence interval 1.3-8.3, p = 0.010). Multivariate analysis that included dense breasts (>50% density), positive margin, no adjuvant radiotherapy, and no adjuvant chemotherapy revealed that dense breasts were significant factors for predicting locoregional recurrence risk (hazard ratio 3.6, 95% confidence interval 1.2-11.1, p = 0.025).

Conclusions: Our results demonstrate that dense breast tissue (>50% density) increased the risk of locoregional recurrence after modified radical mastectomy in patients with invasive breast cancer. Additional prospective studies are necessary to validate these findings.

Trial registration: The study is retrospectively registered with ClinicalTrials.gov, number NCT02771665 , on May 11, 2016.

Keywords: Breast cancer; Case-control study; Distant metastasis; Loco-regional recurrence; Mammographic breast density; Modified radical mastectomy.

Fig. 1

Patient flowchart. Between January 2004 and December 2009, a total of 1056 patients received modified radical mastectomy (MRM) and had pre-operative mammographic breast density (MBD) measured at our institution. Seventy women who received neoadjuvant chemotherapy were excluded. Recurrences were categorized as locoregional (ipsilateral chest wall or axillary, internal mammary, or supraclavicular nodes) or distant metastasis. Each patient with known locoregional recurrence or distant metastasis (n = 121, the case group) were matched to at least one patient without recurrence (the control group) by pathological disease stage, age, and year of diagnosis

Fig. 2

Mammographic breast density measurement using the computer-assisted method. a Left mediolateral oblique projection mammograms were used to assess women with right-sided breast cancer. b A threshold was selected by the operator to isolate the breast from the surrounding background. c A second threshold was set to identify areas of density. d The mammographic breast density (MBD) percentage was determined by measuring the total area of the breast and the number of pixels outlined in the dense regions using the computer software. e The estimated MBD was classified according to the American College of Radiology (ACR) lexicon definition before 2013. Specifically, ACR 1 indicates <25% density and that “the breast is almost entirely fat.” ACR 2 indicates 25–50% density and that “there are scattered fibroglandular tissues.” ACR 3 indicates 50–75% density and that “the breast is heterogeneously dense.” ACR 4 indicates >75% density and that “the breast is extremely dense”