Marion T van Mackelenbergh1,2, Carsten Denkert3, Valentina Nekljudova4, Thomas Karn5, Christian Schem6, Frederik Marmé7, Elmar Stickeler8, Christian Jackisch9, Claus Hanusch10, Jens Huober11, Peter A Fasching12, Jens-Uwe Blohmer3, Sherko Kümmel13, Volkmar Müller14, Andreas Schneeweiss7, Michael Untch15, Gunter von Minckwitz4, Karsten E Weber4, Sibylle Loibl4. 1. German Breast Group, c/o GBG Forschungs GmbH, Martin-Behaim-Straße 12, 63263, Neu-Isenburg, Germany. marion.vanmackelenbergh@gbg.de. 2. Universitätsklinikums Schleswig-Holstein Kiel, Kiel, Germany. marion.vanmackelenbergh@gbg.de. 3. Charite Berlin, Institute of Pathology and German Cancer Consortium (DKTK), Partner Site, Berlin, Germany. 4. German Breast Group, c/o GBG Forschungs GmbH, Martin-Behaim-Straße 12, 63263, Neu-Isenburg, Germany. 5. Universitätsklinikum Frankfurt, Frankfurt, Germany. 6. Universitätsklinikums Schleswig-Holstein Kiel, Kiel, Germany. 7. Universitätsklinikum Heidelberg, Heidelberg, Germany. 8. Universitätsklinikum Aachen, Aachen, Germany. 9. Sana Klinikum Offenbach, Offenbach, Germany. 10. Universitätsklinikum München, Munich, Germany. 11. Universitätsklinikum Ulm, Ulm, Germany. 12. Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany. 13. Kliniken Essen Mitte, Essen, Germany. 14. Universitätsklinikum Hamburg, Hamburg, Germany. 15. Helios Kliniken Berlin-Buch, Berlin, Germany.
Abstract
PURPOSE: The estrogen receptor (ER) is involved in control of progesterone receptor (PgR) expression and lack of PgR may be also a surrogate of altered growth factor signaling. The aim of this study was therefore to investigate PgR expression as predictive factor for response to neoadjuvant therapy and long-term outcome. METHODS: Five thousand and six hundred and thirteen patients with primary breast cancer and positive ER expression from ten German neoadjuvant trials of anthracycline and taxane-based chemotherapy were included. Pathologic complete response (pCR), disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), and local recurrence-free survival (LRFS) were compared according to PgR expression. RESULTS: The lack of PgR expression (1172 patients) was associated with grade 3 (38.4 vs. 26.3%; p < 0.001), nodal involvement (>cN2) (6.8% vs. 4.7%; p = 0.004), and HER2 positivity (36.2 vs. 22.3%; p < 0.001). pCR rates of PgR-negative tumors were higher in the entire cohort (13.8 vs. 7.5%; p < 0.001) and in the HER2-negative subgroup (11.2 vs. 5.8%; p < 0.001). In multivariable logistic regression, PgR negativity was an independent predictive factor for pCR overall (OR 1.76; p < 0.001) and in the HER2-negative patients (OR 1.99; p < 0.001). Patients with PgR-negative disease had significantly worse outcome (p < 0.001, respectively). Multivariable Cox regression analysis revealed that PgR was an independent prognostic factor for DFS, OS, DDFS, and LRFS. CONCLUSION: ER-positive/PgR-negative breast carcinomas are associated with higher response but also worse long-term outcome after neoadjuvant therapy. PgR negativity is an independent predictive factor for pCR after neoadjuvant chemotherapy in ER-positive HER2-negative breast cancer.
PURPOSE: The estrogen receptor (ER) is involved in control of progesterone receptor (PgR) expression and lack of PgR may be also a surrogate of altered growth factor signaling. The aim of this study was therefore to investigate PgR expression as predictive factor for response to neoadjuvant therapy and long-term outcome. METHODS: Five thousand and six hundred and thirteen patients with primary breast cancer and positive ER expression from ten German neoadjuvant trials of anthracycline and taxane-based chemotherapy were included. Pathologic complete response (pCR), disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), and local recurrence-free survival (LRFS) were compared according to PgR expression. RESULTS: The lack of PgR expression (1172 patients) was associated with grade 3 (38.4 vs. 26.3%; p < 0.001), nodal involvement (>cN2) (6.8% vs. 4.7%; p = 0.004), and HER2 positivity (36.2 vs. 22.3%; p < 0.001). pCR rates of PgR-negative tumors were higher in the entire cohort (13.8 vs. 7.5%; p < 0.001) and in the HER2-negative subgroup (11.2 vs. 5.8%; p < 0.001). In multivariable logistic regression, PgR negativity was an independent predictive factor for pCR overall (OR 1.76; p < 0.001) and in the HER2-negative patients (OR 1.99; p < 0.001). Patients with PgR-negative disease had significantly worse outcome (p < 0.001, respectively). Multivariable Cox regression analysis revealed that PgR was an independent prognostic factor for DFS, OS, DDFS, and LRFS. CONCLUSION:ER-positive/PgR-negative breast carcinomas are associated with higher response but also worse long-term outcome after neoadjuvant therapy. PgR negativity is an independent predictive factor for pCR after neoadjuvant chemotherapy in ER-positive HER2-negative breast cancer.
Entities:
Keywords:
Breast cancer; Neoadjuvant chemotherapy; Outcome; Progesterone receptor
Authors: Belén P Solans; Ascensión López-Díaz de Cerio; Arlette Elizalde; Luis Javier Pina; Susana Inogés; Jaime Espinós; Esteban Salgado; Luis Daniel Mejías; Iñaki F Trocóniz; Marta Santisteban Journal: Br J Clin Pharmacol Date: 2019-06-14 Impact factor: 4.335
Authors: M G Davey; É J Ryan; P J Folan; N O'Halloran; M R Boland; M K Barry; K J Sweeney; C M Malone; R J McLaughlin; M J Kerin; A J Lowery Journal: BJS Open Date: 2021-05-07