Abstract 5570: Heterogeneity of luminal breast cancer characterized by immunohistochemical expression of basal markers
Authors: Sung Hyuna , Chang-Claude Jenny , Figueroa Jonine , Nevanlinna Heli , Giles Graham G. , Cox Angelia , Cross Simon S. , Southey Melissa C. , McLean Catriona , Bolla Manjeet K. , Shah Mitul , Dunning Alison M. , Dennis Joe , Wang Qin , Michailidou Kyriaki , Easton Douglas F. , Pharoah Paul D. P. , Sherman Mark E. , Garcia-Closas Montserrat , Yang Xiaohong R. 
Published: August 2015

Data from epidemiologic studies demonstrated that some established breast cancer risk factors such as parity and obesity had differential effect on luminal (estrogen receptor (ER) positive or progesterone receptor (PR) positive, and HER2 negative) and CBP subtypes (ER-, PR-, HER2- and express basal markers [cytokeratin 5/6 (CK5/6) (or CK5) and/or the epidermal growth factor receptor (EGFR)], known as the core basal phenotype), suggesting that luminal and CBP subtypes may have different underlying etiology. Recent data suggest that a subset of ER+ tumors with preexisting CK5+ cells may be resistant to hormone therapies and represent a clinically unique entity. In addition, luminal tumors expressing basal markers (luminal-basal) were associated with poorer prognosis compared to luminal tumors negative for basal markers. To assess whether luminal-basal tumors represent a distinct disease entity from an etiologic perspective, we pooled individual data for 6,112 invasive breast cancer cases contributed by five studies participating in the Breast Cancer Association Consortium (BCAC), with risk factor information and ER, PR, HER2, and basal marker data. We used unconditional logistic regression to evaluate relationships between risk factors and tumor subtypes by comparing luminal-basal tumors (ER+ or PR+, HER2-, CK5/6+ and/or EGFR+) to pure luminal A tumors (ER+ or PR+, HER2-, CK5/6-, EGFR-) in case-only analyses and to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between risk factors and specific tumor subtypes in 3 population-based studies including up to 4,732 cases and 13,242 controls. In case-only analyses, we found that postmenopausal cases with luminal-basal tumors were more likely to be parous (ORparous vs. nulliparous = 1.72; 95% CI = 1.06-2.78; P = 0.03), have higher number of full term births (ORtrend = 1.33; 95% CI = 1.07-1.66; P = 0.01), and lower frequency of obesity (ORBMI≥ 30 kg/m2 vs. &lt;25 kg/m2 = 0.62; 95% CI = 0.40-0.95; P = 0.03) compared to cases with pure luminal A tumors. In case-control analysis, obesity, particularly postmenopausal obesity, was significantly associated with decreased risk of luminal-basal tumors (ORBMI≥ 30 kg/m2 vs. &lt;25 kg/m2 = 0.57; 95% CI = 0.35-0.93; P = 0.02). In contrast, postmenopausal obesity was associated with increased risk of pure luminal A tumors, and premenopausal obesity was associated with increased risk of CBP tumors. In conclusion, our study suggests that luminal-basal cancers are more frequent among lean and parous postmenopausal women than pure luminal A cancers. Future studies with larger number of subjects and detailed annotation of subtype and risk factor information are needed to validate our findings and to more accurately assess etiologic and clinical heterogeneity within luminal A tumors.

Citation Format: Hyuna Sung, Jenny Chang-Claude, Jonine Figueroa, Heli Nevanlinna, Graham G. Giles, Angelia Cox, Simon S. Cross, Melissa C. Southey, Catriona McLean, Manjeet K. Bolla, Mitul Shah, Alison M. Dunning, Joe Dennis, Qin Wang, Kyriaki Michailidou, Douglas F. Easton, Paul D. P. Pharoah, Mark E. Sherman, Montserrat Garcia-Closas, Xiaohong R. Yang. Heterogeneity of luminal breast cancer characterized by immunohistochemical expression of basal markers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5570. doi:10.1158/1538-7445.AM2015-5570