Global breast cancer research makes significant discoveries

The original study was the largest study
in women with known mutations in the breast cancer genes BRCA1 and BRCA2 in the world.
It had two "significant" findings
.

Professor Logan Walker said: "We found a gene called SULT1A1 that can help doctors reduce the risk of breast cancer in women, especially if they also inherit a BRCA1 mutation
.
We also found that women who inherited a deletion in the BRCA1 gene had the highest
risk of breast cancer for reasons that were not yet well understood.
”

The study, conducted in collaboration with the International BRCA1/2 Modifier Research Consortium (CIMBA), involved approximately 26,000 women known to have BRCA1 or BRCA2 gene mutations, as well as 166 researchers
from 160 institutions worldwide.

In New Zealand, one in 250 people inherits mutations in both genes, meaning they are at risk of
breast and ovarian cancer.
However, the risk of cancer in these individuals varies widely due to other unknown genetic changes, which presents significant challenges
for counseling and clinical decision-making.

Currently, the most effective risk-reducing strategy for these high-risk women with breast cancer is bilateral mastectomy
.
Walker said that while this approach works, it is irreversible and causes ongoing psychological and physical damage to patients, especially young women
.

Studies have found that reduced levels of the protein produced by the SULT1A1 gene can reduce the risk of
breast cancer.
The SULT1A1 gene plays an important role
in the metabolism of carcinogens.

"When we reduced the activity of the SULT1A1 gene in breast cells, the cells grew more slowly and became more resistant to DNA damage
.
This cancer-like feature supports epidemiological results
from 26,000 women.
”

The next step is to develop a risk-reducing drug, which will be led
by Dr George Wiggins of the University of Otago.

"Preventive drug therapy is gradually being proven
in preventing different diseases.
For example, aspirin, statins and antihypertensive therapies have had a significant impact
in reducing cardiovascular disease incidence and increasing life expectancy.
In contrast, therapeutic interventions to prevent breast cancer have progressed poorly
.
Providing a non-invasive and easily accessible preventive therapy to women at high risk of breast cancer will bring many benefits
to health systems, patients and their whānau.
This therapy can give genetically predisposed young women the opportunity to have and breastfeed their children
by delaying or replacing risk-reducing surgeries.
”

In New Zealand, breast cancer is the most common cancer among Māori and non-Māori women, with more than 3,300 breast cancer diagnosed and more than 600 deaths
each year.

"For many people, risk-reducing surgery can also be a barrier to breast cancer prevention, leading to inequality
in health outcomes," Walker said.
Effective prevention strategies targeting women at increased risk of breast cancer are essential
to control and reduce the social and economic impact of the disease.
”

The study was funded by the Health Research Council of New Zealand
.

Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers