on Companion Diagnostics). At the same time, the FDA
approved a test to identify the patients for whom olaparib is
approved, the BRACAnalysis CDx.
Olaparib is the first in a new class of agents that target poly
ADP-ribose polymerase (PARP) proteins, which have a key
role in one of the many pathways that cells use to repair
damaged DNA (see Figure 15, p. 74). Therefore, blocking
PARP proteins with olaparib reduces the ability of a cell to
repair damaged DNA.
BRCA1 and BRCA2 have a role in a second DNA repair
pathway, and many BRCA1 and BRCA2 gene mutations
disable this pathway. Thus, the rationale for testing olaparib
as a potential treatment for women with advanced ovarian
cancer who have inherited a BRCA1 or BRCA2 gene
mutation is that having two DNA repair pathways out of
action may mean that the ovarian cancer cells are unable
to repair DNA damage that accumulates as they multiply
(see Developing Cancer, p. 18), and that the accumulating
damage will ultimately cause the cancer cells to die (see
Figure 15, p. 74).
In fact, blocking PARP with olaparib led to tumor shrinkage
or disappearance in a significant number of women with
advanced ovarian cancer who had an inherited BRCA1 or
BRCA2 gene mutation ( 107). It is hoped that future studies
will reveal that olaparib also extends survival for women
with advanced ovarian cancer who inherit a BRCA1 or
BRCA2 gene mutation, like Patty Klein (see p. 72).
Keeping Breast Cancer Cells at Bay
Despite major advances made in treating breast cancer,
the disease remains the second-leading cause of cancer-related death for women in the United States ( 6). One
recent FDA decision has the potential to power even more
progress against breast cancer because it has provided a new
treatment option for certain patients with the disease.
The majority of breast cancers are characterized by the
presence of proteins called hormone receptors. The
growth of these breast cancers is fueled by hormones,
which attach in a lock-and-key fashion to the hormone
receptors on individual breast cancer cells, stimulating
the cells to multiply and survive. This knowledge led to
the development of therapeutics like tamoxifen, which
blocks the hormone estrogen from attaching to its receptor,
and letrozole, which lowers the level of estrogen in the
body. Therapeutics like these have been used extremely
successfully for decades to treat patients with hormone
receptor–positive breast cancer. However, they have limited
clinical benefit if disease progresses.
