TEST:

BROCA Cancer Risk Panel

The high prevalence and heterogenous spectrum of pathogenic variants identified among self-reported African descendants in Northeast Brazil is consistent with studies in other African ancestry populations with a high burden of aggressive young onset breast cancer. It underscores the need to integrate comprehensive cancer risk assessment and genomic testing in the management of newly diagnosed Black women with breast cancer across the African Diaspora, enabling improved cancer control in admixed underserved and understudied populations.

PDX were treated with PARPi rucaparib (300-450mg/kg) and cisplatin (4mg/kg). Our work in PDX provides further evidence that BRCA1 D11q expression can impact on PARPi and platinum responses, and is a clinically relevant mechanism of PARPi resistance in a subset of patients with BRCA1 mutations. Whilst high D11q expression can be associated with secondary BRCA1 splice site mutations (PDX #049 and #217), it can arise independently (PDX #032). Thus, BRCA1 D11q isoform expression should be considered a potential mechanism of acquired PARPi-resistance in patients with BRCA1 exon 10 mutations.

PDX were treated with PARPi rucaparib (300mg/kg) and cisplatin (4mg/kg). Our work in PDX provides additional functional evidence that BRCA1 D11q expression impacts on PARPi and platinum responses, and is a clinically relevant mechanism of PARPi resistance in a subset of patients with BRCA1 mutations. Whilst high D11q expression can be associated with secondary BRCA1 splice site mutations (PDX #1049), it can also occur in their absence (PDX #1032). Thus, BRCA1 D11q isoform expression should be considered a potential mechanism of PARP-resistance in patients with BRCA1 11q mutations.

"This study reveals an unmet clinical need of genetic testing that could benefit a significant proportion of at-risk Latinas. It also highlights the complexity of Hispanic populations as pathogenic factors may originate from any of the ancestral populations that make up their genetic backgrounds."

"Conclusion Among Nigerian women, one in eight cases of invasive breast cancer is a result of inherited mutations in BRCA1, BRCA2, PALB2, or TP53, and breast cancer risks associated with these genes are extremely high. Given limited resources, prevention and early detection services should be especially focused on these highest-risk women."