Maria De Sousa
BIO 194
Professor Rinehart-Kim
Writing assignment #3

Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation

The article referenced in this summary explores and tests whether Olaparib, a poly
polymerase inhibitor can be used to prompt the deceleration of disease progression in patients
with metastatic breast cancer due to germline BRCA gene mutations. BRCA genes 1 and 2, also
known as Breast Cancer genes 1 and 2 are genes responsible for the production of proteins that
repair damaged DNA. They are considered tumor suppressor genes because they regulate cell
division to ensure normal replication, thus preventing cancer. Like with most genes, BRCA 1
and 2 can mutate into different variants, which disrupts their normal function. When a harmful
variant of BRCA is passed down to offspring by either of the parents, the offspring’s chance of
developing cancer increases.
Metastatic cancer is categorized as a type of breast cancer that spreads to an area further
from the one where it started. It is also known as stage 4 cancer, which is the highest stage of a
cancer diagnosis. This stage is reached through a process known as metastasis, where portions of
the tumor break away from the original location and travel to other parts of the body.
Olaparib is a medication that is also known as Lynparza and is widely used for the
treatment of BRCA gene-related cancers. It is thought to be a PARP inhibitor that blocks
proteins that repair damaged DNA. In this case, it is used for cancer treatment because it stops
the repairs of cancer cells’ DNA, leading to cell death. For this specific study, researchers
focused on assessing Olaparib’s effectiveness on progression-free survival compared to standard
treatments, such as chemotherapy.
In order to explore this, a randomized 3-phase study was conducted to compare
Olaparib’s effectiveness by comparing it to standard therapy. The patients chosen had a germline
BRCA mutation and showed no history of more than 2 chemotherapy regimens for metastatic
disease. They were randomly assigned to a group using a 2:1 ratio. One group would receive
300mg Olaparib tablets twice a day, while the other group received standard chemotherapy with
the physician’s choice of drug. At the end of the randomization, 205 patients received the
Olaparib drug and 97 received standard therapy. Every 6 weeks until week 24, magnetic
resonance was done and progression was assessed every week after the first event
Although there was no significant survival observed due to the Olaparib treatment, it was
found that the median survival rate with no disease progression was slightly longer and the
chance of progression was 42% lower than with standard therapy. The trial had some limitations,
including the different types of alternative treatments used for the control groups thus not
specifying differences in effect compared to a certain treatment. Overall, the study included
crucial exploration and hypothesis generation of the potential of Olaparib for the treatment of
BRCA mutation-related cancers.