Two studies published in EBioMedicine could help steer researchers toward alternative prevention strategies for breast and ovarian cancer that render surgery unnecessary.

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Both studies examine the mechanisms behind cancer caused by mutations in the BRCA1 and BRCA2 genes, known for significantly increasing the risk of breast and ovarian cancer.

Both studies reveal new information about the effects of mutations in genes that lead to a very high risk of breast cancer – the most common cancer in women worldwide – and ovarian cancer, the deadliest form of gynecological cancer.

The genes in question are BRCA1 and BRCA2. BRCA1 and BRCA2 mutations account for around 20-25% of all cases of hereditary breast cancer, 5-10% of all cases of breast cancer and around 15% of all cases of ovarian cancer.

At present, women carrying these mutated genes who are identified as being at high risk of these cancers can choose to have preventive surgery – either a double mastectomy or removal of their ovaries and fallopian tubes. For many, however, surgery is not an ideal solution.

“Preventive surgery is quite a drastic measure and we’re unsatisfied with the situation – we are aiming to prevent breast cancer, and findings from our research are a significant step forward in demonstrating the importance of why further research is critical in this arena,” states Prof. Martin Widschwendter, lead author of one of the new studies, from University College London in the UK.

Mutations in the BRCA1 and BRCA2 genes can also affect the ovaries and pituitary gland that regulate the menstrual cycle, with hormones such as progesterone that control the cycle known to influence the development of these cancers.

In the first study, Prof. Widschwendter and colleagues identified that women who have mutations in the BRCA1 or BRCA2 genes have unusually low levels of a molecule called osteoprotegerin (OPG) in their blood. OPG is known to block the effects of a protein called RANKL that is a trigger for breast cancer, whose production is boosted by progesterone.

While women with BRCA1 or BRCA2 mutations did not have increased levels of RANKL in their blood, they did have less OPG. The researchers speculate that a drug which mimics the effect of OPG or inhibits the effects of progesterone could, in turn, reduce breast cancer risk.

“Prevention without surgery is the ultimate goal and this study is the first proof of principle – we have identified a new target we can now use to decrease breast cancer risk,” Prof. Wildschwendter concludes.

For the second study, Prof. Louis Dubeau and colleagues, from the Keck School of Medicine at the University of Southern California in the US, developed a new mouse model to make it easier for researchers to examine the influence of the menstrual cycle on breast and ovarian cancer risk.

Prof. Dubeau explains the impetus for the study:

We know that the menstrual cycle has an effect on the development of these cancers, but we don’t understand the mechanisms behind it. We wanted to develop a mouse model researchers could use to study ways of preventing breast and ovarian cancer in women with BRCA1 and BRCA2 mutations.”

In this model, the researchers engineered mice to carry mutations that corresponded to those affecting the BRCA1 gene in humans.

Fast facts about breast cancer
  • Around 1 in 8 American women will develop invasive breast cancer during their lifetime
  • Breast cancer death rates have been declining since 1989, a fall attributed to earlier detection, screening and awareness
  • There are currently more than 2.8 million breast cancer survivors in the US.

Learn more about breast cancer

These mutations were genetically engineered to occur in tissues associated with increased cancer risk as well as in the ovaries and pituitary gland.

By doing this, the model allows researchers to examine the effects of these mutations on both the menstrual cycle and high-risk tissues independently of each other.

With this mouse model, the researchers discovered that some forms of ovarian cancer originate in tissues located outside the ovaries and fallopian tubes – a discovery that suggests surgical removal of these organs is not guaranteed to prevent this cancer in humans.

“We hope this will result in new approaches that will eliminate the need for surgery in the future,” Prof Dubeau concludes.

Prof. Widschwendter and his team aim to make use of this mouse model to test the effectiveness of OPG in preventing breast cancer. In addition to this, they also hope to trial OPG in patients who are waiting to have preventive surgery, assessing any biological changes in tissues at risk of cancer to determine its potential as a form of cancer prevention.

Previously, Medical News Today reported on a study published in JAMA Oncology questioning whether surgery and radiotherapy are appropriate for women in the earliest stages of breast cancer.