Differences in race, molecular and tumor characteristics among women diagnosed with invasive ductal and lobular breast carcinomas
The dominant invasive breast cancer histologic subtype, ductal carcinoma, shows intrinsic subtype diversity. However, lobular breast cancers are predominantly Luminal A. Both histologic subtypes show distinct relationships with patient and tumor characteristics, but it is unclear if these associations remain after accounting for intrinsic subtype.
Generalized linear models were used to estimate relative frequency differences (RFDs) and 95% confidence intervals (95% CIs) for the associations between age, race, tumor characteristics, immunohistochemistry (IHC) and RNA-based intrinsic subtype, TP53 status, and histologic subtype in the Carolina Breast Cancer Study (CBCS, n = 3,182) and The Cancer Genome Atlas (TCGA, n = 808).
Relative to ductal tumors, lobular tumors were significantly more likely to be Luminal A [CBCS RNA RFD: 44.9%, 95% CI (39.6, 50.1); TCGA: RFD: 50.5%, 95% CI (43.9, 57.1)], were less frequent among young (≤ 50 years) and black women, were larger in size, low grade, less frequently had TP53 pathway defects, and were diagnosed at later stages. These associations persisted among Luminal A tumors (n = 242).
While histology is strongly associated with molecular characteristics, histologic associations with age, race, size, grade, and stage persisted after restricting to Luminal A subtype. Histology may continue to be clinically relevant among Luminal A breast cancers.
KeywordsBreast cancer Histologic subtype Intrinsic subtype
We would like to thank that participants who generously participated in these studies. This work was supported by the Komen Graduate Training and Disparities Research Training Grant (LAW); Komen Career Catalyst Grant (CCR16376756) (KAH); National Institutes of Health: P50 CA058223 and U01 CA179715 (AFO and MAT); R01 HG009125, P01 CA142538, and P30 ES010126 (MIL), and U54 CA156733 (MAT), R01 CA19575401 (CMP).
- 3.Rosen PP (2009) Rosen’s breast pathology, 3rd edn. Lippincott Williams & Wilkins, PhildelphiaGoogle Scholar
- 8.Pestalozzi BC, Zahrieh D, Mallon E et al (2008) Distinct clinical and prognostic features of infiltrating lobular carcinoma of the breast: combined results of 15 International Breast Cancer Study Group clinical trials. J Clin Oncol 26:3006–3014. https://doi.org/10.1200/JCO.2007.14.9336 CrossRefGoogle Scholar
- 13.Badowska-Kozakiewicz AM, Patera J, Sobol M, Przybylski J (2015) The role of oestrogen and progesterone receptors in breast cancer—immunohistochemical evaluation of oestrogen and progesterone receptor expression in invasive breast cancer in women. Współczesna Onkol 3:220–225. https://doi.org/10.5114/wo.2015.51826 CrossRefGoogle Scholar
- 15.Biglia N, Maggiorotto F, Liberale V et al (2013) Clinical-pathologic features, long term-outcome and surgical treatment in a large series of patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). Eur J Surg Oncol 39:455–460. https://doi.org/10.1016/j.ejso.2013.02.007 CrossRefPubMedGoogle Scholar
- 19.García-Fernández A, Lain JM, Chabrera C et al (2015) Comparative long-term study of a large series of patients with invasive ductal carcinoma and invasive lobular carcinoma. Loco-regional recurrence, metastasis, and survival. Breast J 21:533–537. https://doi.org/10.1111/tbj.12455 CrossRefPubMedGoogle Scholar
- 23.Bharat A, Gao F, Margenthaler JA (2009) Tumor characteristics and patient outcomes are similar between invasive lobular and mixed invasive ductal/lobular breast cancers but differ from pure invasive ductal breast cancers. Am J Surg 198:516–519. https://doi.org/10.1016/j.amjsurg.2009.06.005 CrossRefPubMedGoogle Scholar
- 25.Conners AL, Jones KN, Hruska CB et al (2015) Direct-conversion molecular breast imaging of invasive breast cancer: imaging features, extent of invasive disease, and comparison between invasive ductal and lobular histology. Am J Roentgenol 205:W374–W381. https://doi.org/10.2214/AJR.14.13502 CrossRefGoogle Scholar
- 26.Tavassoli F, Schnitt SJ, Hoefler H et al (2003) Intraductal proliferative lesions. In: Tavassoli F, Devilee P (eds) World Health Organization classification of tumours. Pathology and genetics of tumours of the breast and female genital organs. IARC Press, Lyon, pp 63–74Google Scholar
- 43.Taylor NJ, Nikolaishvili-Feinberg N, Midkiff BR et al (2015) Rational manual and automated scoring thresholds for the immunohistochemical detection of TP53 missense mutations in human breast carcinomas. Appl Immunohistochem Mol Morphol 24:1–7Google Scholar
- 48.Lim ST, Yu JH, Park HK et al (2014) A comparison of the clinical outcomes of patients with invasive lobular carcinoma and invasive ductal carcinoma of the breast according to molecular subtype in a Korean population. World J Surg Oncol 12:56. https://doi.org/10.1186/1477-7819-12-56 CrossRefPubMedPubMedCentralGoogle Scholar