Abstract P2-03-09: Comparison of the mutational landscape of breast cancer during pregnancy and non-pregnant controls
Authors: Loibl S , Pfarr N , Weber K , Neunhöffer T , Villegas S , Stenzinger A , Furlanetto J , Aktas B , Budczies J , Marmé F , Kahmann L , Denkert C , Weichert W 
Published: March 2017

Background:Currently, breast cancer during pregnancy (BCP) is not believed to be biologically different from breast cancer unrelated to pregnancy based on limited datasets mainly obtained by immunohistochemistry. However, some groups report that BCP patients have an inferior survival compared to young non-pregnant breast cancer patients. The largest analysis based on the BCP registry by the German Breast Group (GBG) revealed however, no difference between pregnant and non-pregnant breast cancer patients, indicating that treatment rather than biology might be the reason for the inferior survival reported by others.

Methods: The BCP study (GBG 29/BIG 03-02) is a multicentre observational study for breast cancer during pregnancy. In tumour tissue collected within this study from pregnant M0 patients we investigated the following genes: AKT1, ATM, BRAF, CBFB, CCND1, CDH1, CDKN2A, CTCF, EGFR, ERBB2, ESR1, FGFR2, GATA3, KRAS, MAP2K4, MAP3K1, MDM2, MED12, MYC, PIK3CA, PIK3R1, PTEN, RB1, RUNX1, and TP53 by massive parallel sequencing (MPS). This included patients with all molecular subtypes: HR+/-, HER2+/-. Sequencing was done on an IonTorrent Proton using a custom designed Breast Cancer Panel (BCPv2). This panel comprises 236 amplicons split into two primer pools and covers hotspot regions of 138 exons of the 25 genes.

To test the hypothesis that breast cancer diagnosed during pregnancy is biologically not different from breast cancer diagnosed in young non-pregnant women, we compared the molecular profiles obtained, with genetic data from M0 patients not known to be pregnant from TCGA with age &lt;= 45. TCGA data were pre-processed to be compatible to the targeted MPS datasets from pregnant patient.

Results: Material from 141 patients from the BCP study was available from which ultimately 109 fully evaluable MPS datasets could be obtained. In the TCGA data set 114 breast cancer patients &lt;= 45 years could be identified. Pregnant patients with breast cancer were significantly younger, had more often HR- tumours (59.6% vs 30.1%) but had less frequently grade 3 tumours (30.6% vs 48.2%). All other clinical variables showed no significant differences between pregnant and non-pregnant patients. In the BCP data, overall 106 mutations could be found. The most frequent mutations were detected in TP53 (62%) and in PIK3CA (11.1%). In non-pregnant patients the mutation rates were different with 32.5% in TP53 and 21.1% in PIK3CA.

Exact matching by variables age, HR, HER2 and grade yielded 40 patients from both datasets. In these subcohorts, still divergent mutational rates for TP53 and PIK3CA between pregnant and non-pregnant women were noted, however, the differences failed to reach statistical significance.

Conclusions: Overall the mutational landscapes do not seem to be overtly different between pregnant patients and no-pregnant controls, although slight imbalances in mutational rates occurred, which might be partly explained by a selection bias and a small sample size after matching. Further comparisons using other datasets, looking into survival and regarding copy number variation are currently conducted.

This research is been funded by the German Cancer Consortium-DKTK and the BANSS Foundation.

Citation Format: Loibl S, Pfarr N, Weber K, Neunhöffer T, Villegas S, Stenzinger A, Furlanetto J, Aktas B, Budczies J, Marmé F, Kahmann L, Denkert C, Weichert W. Comparison of the mutational landscape of breast cancer during pregnancy and non-pregnant controls [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 P2-03-09.