Abstract P6-09-12: A consecutive series of early breast cancers with a low estrogen receptor expression
Authors: Paredis D , Wildiers H , Vergote I , Smeets A , Van Limbergen E , Remmerie C , Laenen A , Jongen L , Floris G , Neven P 
Published: March 2017

Background: Estrogen receptor (ER) positivity is not a dichotomous biological phenomenon and within the ER positive cohort, major differences in amount and percentage of ER expression are observed. Women with tumors expressing low ER levels have worse outcome as quantitative ER (qER) expression is predictive for benefit from hormone therapy. The aim of our study was to further characterize these patients, tumors and the distant relapse free survival (D-RFS) based upon qER expression.

Patients and Methods: In this retrospective study we included women with primary operable human epidermal growth factor receptor 2 (HER2) negative breast cancers, diagnosed between January 1st 2000 and September 30th 2015 in the Multidisciplinary Breast Center of University Hospital of Leuven. ER-low tumors ((1-33% immunohistochemical (IHC)staining, Allred proportion score (2-3/5), or H-score (&lt;100/300 + &lt;33% staining)) were compared with ER-high tumors((&gt; 33% IHC staining, Allred proportion score (4-5/5), or H-score ≥ 100/300)) and triple negative (TN) tumors (Allred proportion score (0-1/5) or H-score 0% staining). PR and HER2 were scored according to ASCO/CAP guidelines. Local and adjuvant therapies were given according to the in house guidelines. The Fisher exact text was used for comparing groups on categorical variables and the Kruskal Wallis test or Mann-Whitney test were used for continuous variables. The Kaplan-Meier method was used for estimating the interval to relapse. The log rank test was used for the comparison between groups (2-sided test with 5% significance, SAS software version 9.4).

Results: A total of 5390 women were included, 115 (2 %) were ER-low, 4658 (86.5%) were ER-high and 617 (11.5%) were TN. Average follow-up was 6 years. Patients with ER-low and TN breast tumors were younger at diagnosis compared to patients with ER-high tumors (respectively 55.5y and 56.7y vs 59.3 y; p&lt;0.001). Tumor size and nodal status did not differ between the three subgroups. ER low and TN were more often grade 3 (61% and 89% vs 24%, p&lt;0.001) which led to a higher mean NPI. Adjuvant chemotherapy was more likely to be given in ER-low and TN cases (57% and 75% vs 26%, p&lt;0.001). Women with an ER-low and TN breast cancer were more often referred for BRCA1/2/CHEK-2 testing as compared to those with an ER-high tumor (respectively 21%, 22% vs 10% p&lt;0.001); a mutation was found 5 to 7 times more in the ER low and TN group (5%-7% vs 1% p&lt;0.001). Metastatic relapse was 18% in ER low (21/114 patients), 15% in TN (90/617 patients) and 6% in ER high (283/4658 patients). Using a Kaplan Meier curve, the 5 year D-RFS was 84%, 85% and 96% in ER-low, TN and ER-high cases. The 10 year D-RFS was respectively 76%, 84% and 91% (p&lt;0.001).

Conclusion: ER-low breast cancers are rare and correlate better with TN than ER-high tumors regarding demographics, tumor grade, BRCA1/2/CHEK-2 mutation risk and breast cancer outcome.Background: Estrogen receptor (ER) positivity is not a dichotomous biological phenomenon and within the ER positive cohort, major differences in amount and percentage of ER expression are observed. Women with tumors expressing low ER levels have worse outcome as quantitative ER (qER) expression is predictive for benefit from hormone therapy. The aim of our study was to further characterize these patients, tumors and the distant relapse free survival (D-RFS) based upon qER expression.

Patients and Methods: In this retrospective study we included women with primary operable human epidermal growth factor receptor 2 (HER2) negative breast cancers, diagnosed between January 1st 2000 and September 30th 2015 in the Multidisciplinary Breast Center of University Hospital of Leuven. ER-low tumors ((1-33% immunohistochemical (IHC)staining, Allred proportion score (2-3/5), or H-score (&lt;100/300 + &lt;33% staining)) were compared with ER-high tumors((&gt; 33% IHC staining, Allred proportion score (4-5/5), or H-score ≥ 100/300)) and triple negative (TN) tumors (Allred proportion score (0-1/5) or H-score 0% staining). PR and HER2 were scored according to ASCO/CAP guidelines. Local and adjuvant therapies were given according to the in house guidelines. The Fisher exact text was used for comparing groups on categorical variables and the Kruskal Wallis test or Mann-Whitney test were used for continuous variables. The Kaplan-Meier method was used for estimating the interval to relapse. The log rank test was used for the comparison between groups (2-sided test with 5% significance, SAS software version 9.4).

Results: A total of 5390 women were included, 115 (2 %) were ER-low, 4658 (86.5%) were ER-high and 617 (11.5%) were TN. Average follow-up was 6 years. Patients with ER-low and TN breast tumors were younger at diagnosis compared to patients with ER-high tumors (respectively 55.5y and 56.7y vs 59.3 y; p&lt;0.001). Tumor size and nodal status did not differ between the three subgroups. ER low and TN were more often grade 3 (61% and 89% vs 24%, p&lt;0.001) which led to a higher mean NPI. Adjuvant chemotherapy was more likely to be given in ER-low and TN cases (57% and 75% vs 26%, p&lt;0.001). Women with an ER-low and TN breast cancer were more often referred for BRCA1/2/CHEK-2 testing as compared to those with an ER-high tumor (respectively 21%, 22% vs 10% p&lt;0.001); a mutation was found 5 to 7 times more in the ER low and TN group (5%-7% vs 1% p&lt;0.001). Metastatic relapse was 18% in ER low (21/114 patients), 15% in TN (90/617 patients) and 6% in ER high (283/4658 patients). Using a Kaplan Meier curve, the 5 year D-RFS was 84%, 85% and 96% in ER-low, TN and ER-high cases. The 10 year D-RFS was respectively 76%, 84% and 91% (p&lt;0.001).

Conclusion: ER-low breast cancers are rare and correlate better with TN than ER-high tumors regarding demographics, tumor grade, BRCA1/2/CHEK-2 mutation risk and breast cancer outcome.

Citation Format: Paredis D, Wildiers H, Vergote I, Smeets A, Van Limbergen E, Remmerie C, Laenen A, Jongen L, Floris G, Neven P. A consecutive series of early breast cancers with a low estrogen receptor expression [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-12.