Gestational breast cancer: distinctive molecular and clinico-epidemiological features. GEICAM/2012-03 study

Incidence of gestational breast cancer (GBC) (during pregnancy, lactation or first year postpartum) ranges from 6-15% of BC in the 20-44 subgroup age. GBC is associated with positive nodes, negative hormonal receptors (HR), triple negative and high grade tumors but little is known at molecular level. We explore specific genomic profiles and clinico-epidemiological features of GBC. Expression of 105 genes was assessed in 50 evaluable tumors from 70 GBC Spanish patients using nCounter platform. The following signatures were assessed: 1) Intrinsic subtypes; 2) Proliferation (P) and Risk of Recurrence (ROR) scores; 3) Claudin-low and 4) Chemo-Endocrine Sensitivity Predictor (CESP). Genomic profile and clinico-epidemiological data were compared to equivalent nonGBC cohorts from GEICAM/9906 (n = 293) (NCT00129922), Málaga (n = 96) (Cancer Res, 2016 76; P3 07 15) and Alamo III project (n = 1473). Out of the 70 patients, 43% were diagnosed during pregnancy and 57% postpartum. The table reports patient and tumor characteristics:Tabled 1n (%)GBCAlamo III9906MálagaMean age at diagnosis35373737Negative HR30 (43)330 (24)33 (16)27 (28)T2-T451 (76)787 (56)176 (60)84 (92)Grade 338 (63)479 (40)121 (44)38 (47)Ki67 (≥20%)33 (89)209 (61)46 (22)60 (64)Family history of BC32 (47)296 (25)--Mean age at first partum3126-- Open table in a new tab Intrinsic subtypes in GBC were 44% Basal-like, 22% Her2-enriched, 20% Luminal B and 14% Luminal A; no Claudin-low tumors were identified. Basal-like phenotype was enriched (44% vs 14%, p < 0.01) and Luminal A was less prevalent (14% vs 28%, p = 0.02) in GBC compared to GEICAM/9906 and Málaga combined dataset. Moreover, GBC showed a lower CESP score (-0.49 vs 0.04) and higher prevalence of ROR-P high risk group (62% vs 41%) than nonGBC cohorts (p ≤ 0.01). Luminal B GBC cases were younger at first partum than Luminal A and Her2 (p = 0.02). Compared to Alamo III, GBC had worse disease free (68% vs 77%, p = 0.01) and overall survival at 5 years (78% vs 91%, p < 0.01). GBC differential biology is suggested by higher Basal-like and lower Luminal A rates, and absence of Claudin-low phenotype, correlating with worse survival and a more aggressive clinico-pathological profile confirmed by a higher ROR-P high rate and lower CESP score.