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.

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.

• Authors: Marion T van Mackelenbergh, Carsten Denkert, Valentina Nekljudova, Thomas Karn, Christian Schem, Frederik Marmé, 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
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 167 Issue 1 Pg. 59-71 (01 2018) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 28875243 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Bridged-Ring Compounds
• Receptors, Estrogen
• Receptors, Progesterone
• Taxoids
• taxane
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Adult
• Aged
• Biomarkers, Tumor (genetics)
• Breast Neoplasms (epidemiology, genetics, pathology)
• Bridged-Ring Compounds (administration & dosage, adverse effects)
• Disease-Free Survival
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Middle Aged
• Neoplasm Recurrence, Local (epidemiology, genetics, pathology)
• Proportional Hazards Models
• Randomized Controlled Trials as Topic
• Receptor, ErbB-2 (genetics)
• Receptors, Estrogen (genetics)
• Receptors, Progesterone (genetics)
• Taxoids (administration & dosage, adverse effects)