RSNA: A magnetic resonance spectroscopy (MRS) technique that monitors
biochemical changes in tissue could improve the management of women at
risk of breast cancer, according to a new study published online in the
journal Radiology.
Many women face a higher risk of breast cancer due to the presence of
BRCA gene mutations. A BRCA1 or BRCA2 mutation carrier has
approximately a 50 percent risk of developing breast cancer before the
age of 50, and the cancer can develop within months of a negative
screening by mammography. The risk is so significant that many women
with BRCA mutations undergo prophylactic, or preventive mastectomies to
avoid getting invasive cancer later in life.
For the new study, researchers assessed 2-D localized correlated
spectroscopy (L-COSY) as a noninvasive means to identify biochemical
changes associated with a very early stage of cancer development known
as the pre-invasive state.
The researchers performed L-COSY on nine women carrying the BRCA1 and
14 women with BRCA2 gene mutations and compared the results with those
from 10 healthy controls who had no family history of breast cancer. All
the patients underwent contrast enhanced 3-T MRI and ultrasound.
While no abnormality was recorded by MRI or ultrasound, L-COSY MRS
identified statistically significant biochemical changes in women with
BRCA1 and BRCA2 gene mutations compared to controls. The researchers
found multiple distinct cellular changes measurable through L-COSY
indicative of premalignant changes in women carrying BRCA gene
mutations.
"These changes appear to represent a series of early warning signs
that may allow women to make informed decisions as to when and if they
have prophylactic mastectomy," said Carolyn Mountford, M.Sc., D.Phil.,
from the University of Newcastle in Callaghan, Australia, Brigham and
Women's Hospital in Boston and the Translational Research Institute in
Brisbane.
Study co-author David Clark, M.B.B.S., B.Sc., F.R.A.C.S., from the
Breast and Endocrine Centre in Gateshead, New South Wales, Australia,
believes the protocol may help guide treatment decisions in women with
BRCA mutations. Dr. Clark noted that approximately half the women who
have BRCA mutations may not develop breast cancer at all and certainly
not before they turn 50 years old, so the spectroscopy technique could
be extremely useful.
"We think there are three stages of pre-cancer progression in the
breast tissue," he said. "Women at Stage 1 could monitor their breasts
with follow-up spectroscopy every six months."
The research team also found evidence that lipid pathways are
affected differently in the two different gene mutations, which may help
explain why BRCA2 mutation carriers survive longer than BRCA1 carriers.
The study represents the culmination of more than 25 years of work,
according to Dr. Mountford. Research on biopsy samples in the 1980s
proved the existence of pre-invasive states, but technological
improvements were needed before the technique could be applied to
clinical MRI scanners.
"It took a multidisciplinary team, including an MR physicist,
chemists, radiographers and radiologists to be sure that what we were
seeing was not apparent from conventional contrast-enhanced imaging,"
Dr. Mountford said.
The researchers hope to confirm the findings in larger populations
and continue to monitor the women in the study group with the 2-D L-COSY
protocol to learn more about the biochemical changes and what they
represent.