119P - Genetic profiling of breast cancer in a developing country: Towards the establishment of oncogenetics in Cameroon

Background

Breast cancer is a highly heterogeneous disease characterised by an accumulation of multiple molecular mutations and is known to have a familial predisposition. The genomic basis of breast cancer in Africans remains mostly uncharacterized. We aimed to characterize the mutational profile of breast cancer in our context, as first steps to the establishment of oncogenetics in our setting.

Methods

Patients with breast cancer visiting two major treatment centres from May 1 to July 31 2022, aged ≥ 75, providing informed consent, and without previous genetic testing were recruited. After pre-test counselling, 5 mL of saliva was collected in Color genomics testing kits and shipped to Color genomics USA. NGS testing for 29 genes (APC, ATM, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A (p14ARF), CDKN2A (p16INK4a), CHEK2, EPCAM, GREM1, MITF, MLH1, MSH6, MSH2, MUTYH, PALB2, PMS, POLD1, POLE, PTEN, RAD51C, SMAD4, STK11, TP53) was performed. The frequency of pathogenic/likely pathogenic (P/LP) mutations was recorded.

Results

There were 82 female breast cancer patients with a mean age of 42.95 ± 11.10 (range 19–71) years. Four (4.88%) had bilateral breast cancer and one (1.21%) had metachronous bilateral breast and ovarian cancer. Fifty-one (62.20%) had a family history of cancer. Overall 23 (28.05%) had a P mutation testing result: BRCA1 (15/82, 18.29%), BRCA2 (2/82, 2.44%), PALB2, ATM, PMS2, and MSH2 (1, 1.22% each). Of the 15 BRCA1 P mutations, 7 (46.67%) were c.4484G>T(p.Arg1495Met), and 3 (20%) c.5155dup(p.Val1719Glyfs*6). One patient had a LP mutation in BRCA1. Twenty-one (25.61%) had a VUS; 2 occurred twice each (APC and PALB2). Both patients with the repeating APC VUS (c.3760A>G(p.Ile1254Val) had extensive family histories of cancer. One of these patients concomitantly had the most frequent BRCA1 mutation: c.4484G>T. Both patients with the repeating PALB2 mutation had extensive family histories of cancer and all had the most frequent BRCA1 mutation: c.4484G>T.

Conclusions

The frequency of P mutations among Cameroonian breast cancer patients is high. This adds to the genomic landscape of cancer in Africa and is ground-breaking work for oncogenetics in the country.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Subgrant of the NIH through the University of Chicago.

Disclosure

All authors have declared no conflicts of interest.