Individuals
who carry a mutation in breast cancer susceptibility gene(BRCA1) are highly
prone to develop breast cancer. As
compared to general population who have 8% chance of developing breast cancer, women
who harbor this germline mutation have a 55-65% chance of developing breast
cancer by the age 70.[1]
These women
frequently undergo prophylactic risk reducing surgeries ( (bilateral
prophylactic mastectomy and bilateral prophylactic salpingo-oophorectomy)
to minimize the chances of developing breast cancer.[2]
Scientist
around the world are long looking for chemoprevention to reduce the risk of cancer
in BRCA1 mutation carriers. Currently Tamoxifen is in use for chemoprevention.
A recent
paper published in Nature[3]
offers a breakthrough for millions of next generation women with BRCA1 mutation
carrier. Researchers are already considering it as ‘holy grail’ of breast
cancer prevention.
Denosumab is
a human monoclonal antibody for the treatment
of osteoporosis. It is also a RANKL signaling
inhibitor, RANK+ and RANK− are two subsets
of luminal progenitors present in the histological normal breast tissue of
BRCA1 mutation carriers. RANK+ cells are highly proliferative,
have grossly aberrant DNA repair and bear a molecular signature similar to that
of basal-like breast cancer. Denosumab inhibited the RANK+ signaling
and stopped the progesterone induced proliferation of pre-neoplastic cells and
also tissues from breast biopsies of BRCA1 mutation carriers. The same effect
was also seen in mouse model of mammary tumorigenesis. Denosumab is already in
use for treatment of osteoporosis and for patients with bone metastasis of
breast cancer.
Geoff
Lindeman, a clinician-scientist at the Walter and Eliza Hall Institute and
a co-author of the study said "Over
the last few years, it has become increasingly clear from the work of several
groups that RANK ligand, which switches on RANK, is an important regulator of
cell growth in the breast. We have now been able to pinpoint the precise
culprit cells and were very excited to see that they express the RANK protein."
As a part of
pilot study three women were also treated with Denosumab and the results are encouraging
days Dr. Lindeman.
Dr.
Francisco Esteva (researcher at NYU Langone Medical Center and a part of the
pilot study) and his colleagues are looking forward to conducting large
scale clinical trials. "The new study does not change any management or
clinical use of any drugs at this point, but it provides data that can be
tested in a clinical trial," he said. "The data are compelling."
He also
added that we are looking at least 10 years down the lane, but it offers hope
for future generations of women.
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