Abstract:
Introduction: Obtaining informed consent from study participants and disseminating
the findings responsibly is a key principle required for ethically conducted clinical and
genetic research. Reports from African researchers providing feedback on insights
gained during the return of whole exome sequencing (WES) results to breast cancer
patients treated in resource-limited settings is lacking.
Aim: The empirical process used to fill this gap in relation to BRCA1/2 variant detection
using WES provided unique insights incorporated into a pathology-supported genetic
testing algorithm for return of research results to Kenyan breast cancer patients.
Methods: The Informed consent form approved by the Moi Teaching and Referral
Hospital in Kenya was adopted from a translational research study conducted in
South Africa. Initially, the informed consent process was piloted in 16 Kenyan female
patients referred for breast surgery, following a community-based awareness campaign.
A total of 95 female and two male breast cancer patients were enrolled in the study
from 2013 to 2016. Immunohistochemistry (IHC) results of estrogen receptor (ER),
progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2)
status were obtained from hospital records. DNA of patients with a family history of
cancer was extracted from saliva and screened for pathogenic variants in the BRCA1/2
genes as the first step using WES.
Results: Ten patients approached for participation in this study declined to sign the
informed consent form. Data on IHC used as a proxy for molecular subtype were
available in 8 of 13 breast cancer patients (62%) with a family history of cancer.
Five BRCA1/2 variants of uncertain clinical significance were detected, as well as a
pathogenic BRCA2 variant (c.5159C > A; S1720∗) in a female patient eligible for
return of WES results.Conclusion: Experience gained during the qualitative pilot phase was essential to
overcome challenges associated with the translation of sophisticated genetic terms
into native African languages. Detection of a pathogenic BRCA2 variant in a patient
with familial breast cancer, frequently associated with hormone receptor-positive breast
carcinoma as reported in this case, led to a high level of confidence on which
to base risk management in future. Implementation of new technologies alongside
standard pathology provides a practical approach to the application of genomic
medicine in Africa.
