Clinicopathological Features and Outcomes Comparing Patients With Invasive Ductal and Lobular Breast Cancer

Abstract

Background: There is increasing interest in better understanding the biology and clinical presentation of invasive lobular cancer (ILC), which is the most common special histological subtype of breast cancer. Limited large contemporary data sets are available allowing comparison of clinicopathologic features between ILC and invasive ductal cancer (IDC).

Methods: The Great Lakes Breast Cancer Consortium was formed to compare clinical behavior of ILC (n = 3617) and IDC (n = 30 045) from 33 662 patients treated between 1990 and 2017 at 3 large clinical centers. We used Kaplan-Meier analysis, Cox proportional hazards modeling, and propensity score matching to evaluate treatment differences and outcomes. All statistical testing used 2-sided P values.

Results: Compared with IDC, patients with ILC were more frequently diagnosed at later stages and with more lymph node involvement (corrected P < .001). Estrogen receptor-positive ILCs were of lower grade (grade 1 and 2: 90% in ILC vs 72% in IDC) but larger in size (T3 and 4: 14.3% in ILC vs 3.4% in IDC) (corrected P < .001), and since 1990, the mean ILC size detected at diagnosis increased yearly. Patients with estrogen receptor (ER)-positive ILC underwent statistically significantly more mastectomies compared with ER-positive IDC (57% vs 46%). Using Kaplan-Meier analysis, patients with ER-positive ILC had statistically significantly worse disease-free survival and overall survival than ER-positive IDC although 6 times more IDCs were classified as high risk by OncotypeDx Breast Recurrence Score assay.

Conclusions: This large, retrospective, collaborative analysis with 3 clinical centers identified meaningful differences in clinicopathological features between ILC and IDC, providing further evidence that these are 2 different entities requiring different clinical management.

Figure 1.

CONSORT diagram. CONSORT diagram of the patients included in the Great Lakes Breast Cancer (GLBC) study showing the filtering steps used to arrive at the final cohort and breakdown of participants by originating institution. CCF = Cleveland Clinic Foundation; HCC = Hillman Cancer Center; ICD = International Classification of Diseases; IDC = invasive ductal carcinoma; ILC = invasive lobular carcinoma; MWH = Magee Womens Hospital; OSUCCC = Ohio State University Comprehensive Cancer Center; UPMC = University of Pittsburgh Medical Center.

Figure 2.

DFS and OS of patients with IDC and ILC. A) A total of 32 306 records in the cohort (28 793 patients with IDC and 3513 patients with ILC) are included for DFS analysis with the median follow-up time of 5.03 years. Log-rank tests were used. Specifically, the 5-, 10-, 15-, and 20-year DFS probabilities for women diagnosed with ER-positive ILC and ER-positive IDC were 94%, 86%, 77%, and 72%, and 94%, 89%, 86%, and 83%, respectively. A total of 33 655 records in the whole cohort (30 039 patients with IDC and 3616 patients with ILC) are included for OS analysis with the median follow-up time of 5.46 years. The estimated 10-year OS probabilities are 0.733 (95% CI = 0.726 to 0.739) for patients with IDC and 0.696 (95% CI = 0.676 to 0.717) for patients with ILC (P < .0001). B) A total of 19 603 records in the ER-positive cohort (17 054 patients with IDC and 2549 patients with ILC) are included for DFS analysis with the median follow-up time of 4.75 years. Log-rank tests were used. A total of 19 787 records in the ER-positive cohort (17 224 patients with IDC and 2563 patients with ILC) are included for OS analysis with the median follow-up time of 5 years. The estimated 10-year OS probabilities are 0.771 (95% CI = 0.762 to 0.781) for patients with IDC and 0.720 (95% CI = 0.694 to 0.748) for patients with ILC (P < .0001). C) DFS and OS comparing patients with IDC and ILC stratified by menopausal status (unadjusted for other covariates using the Kaplan-Meier method). CI = confidence interval; DFS = disease-free survival; ER+ = estrogen receptor positive; IDC = invasive ductal cancer; ILC = invasive lobular carcinoma; OS = overall survival; pre = premenopausal; post = postmenopausal.

Figure 3.

Survival curves stratified by Oncotype Dx TAILORx RS result. Oncotype DX test status is identified as low and intermediate if the RS result is ≤25 and identified as high if the RS result is >25 according to the TAILORx trial groups. DFS and OS analysis (A) in patients with ER-positive disease, (B) in patients with ER-positive IDC, and (C) in patients with ER-positive ILC. Log-rank tests were used to compare the curves (unadjusted for other covariates using the Kaplan-Meier method). DFS = disease-free survival; ER+ = estrogen receptor positive; IDC = invasive ductal cancer; ILC = invasive lobular carcinoma; OS = overall survival; RS = recurrence score.

Figure 4.

Site of recurrence in patients with ER-positive metastatic breast cancer. The bars represent proportion of patients with ER-positive IDC or ER-positive ILC who have recorded information on metastases with recurrence to specific sites as indicated. A 2-sided χ² test was used. CNS = central nervous system; ER = estrogen receptor; IDC = invasive ductal cancer; ILC = invasive lobular carcinoma; LN = lymph node.

Figure 5.

Change over time in histology type, tumor size, and treatment types in patients with ER-positive disease from 1990 to 2017. A) Shows the frequency of histology types in 19 788 patients with ER-positive from 1990 to 2017. B) Shows the trend of tumor size (averaged for each year) in UPMC cohort for 10 495 patients with ER-positive from 1990 to 2017. The mean tumor sizes are 20.58 mm for IDC and 27.64 mm for ILC in 1990 and 19.32 mm for IDC and 30.56 mm for ILC in 2017. C) Shows trends of surgery rates across years for 19 462 patients with ER-positive IDC and ER-positive ILC in 3 sites from 1990 to 2017. There were 9480 patients who had lumpectomy and 9204 patients had mastectomy. D) Shows trends of radiation therapy rates across years for 19 480 patients with ER-positive IDC and ER-positive ILC in 3 sites from 1990 to 2017. In total, 12 392 patients received radiation therapy. E) Shows the trend of hormone therapy rates across years for 19 406 patients with ER-positive IDC and ER-positive ILC in 3 sites from 1990 to 2017. In total, 16 998 patients received hormone therapy. F) Shows the trend of chemotherapy rates across years for 18 876 patients with ER-positive IDC and ER-positive ILC in 3 sites from 1990 to 2017. In total, 7750 patients received chemotherapy therapy. ER+ = estrogen receptor positive; IDC = invasive ductal cancer; ILC = invasive lobular carcinoma; UPMC = University of Pittsburgh Medical Center.