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Outcome after neoadjuvant chemotherapy in estrogen receptor-positive and progesterone receptor-negative breast cancer patients: a pooled analysis of individual patient data from ten prospectively randomized controlled neoadjuvant trials

Marion T Van Mackelenbergh, Carsten Denkert, Valentina Nekljudova, Thomas Karn, Christian Schem, Frederik Marme, Elmar Stickeler, Christian Jackisch, Claus Hanusch, Jens Huober, Peter A Fasching, Jens-Uwe Blohmer, Sherko Kümmel, Volkmar Müller, Andreas Schneeweiss, Michael Untch, Gunter Von Minckwitz, Karsten E Weber & Sibylle Loibl

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.
   
citation van Mackelenbergh M T, Denkert C, Nekljudova V, Karn T, Schem C, Marme F, Stickeler E, Jackisch C, Hanusch C, Huober J, Fasching P A, Blohmer J U, Kümmel S, Müller V, Schneeweiss A, Untch M, von Minckwitz G, Weber K E, Loibl S. Outcome after neoadjuvant chemotherapy in estrogen receptor-positive and progesterone receptor-negative breast cancer patients: a pooled analysis of individual patient data from ten prospectively randomized controlled neoadjuvant trials. Breast Cancer Res Treat 2017; 167:59-71.
   
type journal paper/review (English)
date of publishing 05-09-2017
journal title Breast Cancer Res Treat (167/1)
ISSN electronic 1573-7217
pages 59-71
PubMed 28875243
DOI 10.1007/s10549-017-4480-5