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Breast cancer gene mutations may also lead to heart problems: studies

12/20/2011 11:01 EST | Updated 02/19/2012 05:12 EST
TORONTO - Two gene mutations known to put women who carry them at significantly higher risk of developing breast and ovarian cancers may also predispose those same women to heart disease, a pair of new studies suggest.

The work, done by researchers from Toronto's St. Michael's Hospital, points to the BRCA1 and BRCA2 genes as playing a key role in the body's ability to repair damaged DNA, not just in the breasts and ovaries.

The bodies of women who have a mutated copy of one of the genes may be less well equipped to deal with the DNA damage that humans undergo daily, said Dr. Subodh Verma, a cardiac surgeon and researcher at the hospital who led the team responsible for both studies.

"This may suggest that in addition to a risk of developing breast and ovarian cancer, such individuals may be at a previously unrecognized risk of developing heart failure and heart disease,'' Verma said in an interview.

"It's something that is quite striking and I think it will pave the way now for more focused evaluation of this problem."

The studies were published in the journals Nature Communications and the Journal of Biological Chemistry.

The latter study, which looked at the BRCA2 gene, suggested that a chemotherapy drug commonly used to treat breast cancer may aggravate the heart damage these women sustain. The drug is called doxorubicin; it is a mainstay of breast cancer treatment.

Oncologists may want to rethink how much doxorubicin they give women with these mutations, or consider alternative therapies, oncologist Dr. Christine Brezden-Masley, a co-author of the papers, said in a press release.

But a leading breast cancer researcher said it's premature to give any advice on that score.

Dr. Steven Narod, head of breast cancer research at Women's College Hospital Research Institute in Toronto, pointed out that the studies were done in mice and further work is needed. (Human heart tissues were also used in some of the work.)

"No mice study on its own is sufficient to make a change in clinical practical. It does give us directions towards doing different experiments," said Narod, a recognized expert in BRCA1 and BRCA2 research.

"The research as it is is well done and I don't say that it's not true. I'm just saying when can we go beyond the paper and extrapolate to what would be the situation in humans."

Narod said doxorubicin is an effective drug, one that actually seems to be more efficacious in women with these mutations.

Interestingly, Narod recently published a study that may support the findings of Verma's team. He and colleagues reported that women with the BRCA1 mutation who developed breast cancer and underwent chemotherapy for it went on to develop diabetes at a substantially higher rate than women in the general population.

They developed diabetes — a risk factor for heart disease — at about double the rate of other women in the general population. And if the women were overweight, their risk of developing diabetes after chemotherapy for breast cancer was six times higher than for women without the mutation.

Narod said he could not explain the unexpected finding.

Verma's work points to the possibility that damage done to the heart cannot be properly repaired when the proteins made by the BRCA1 and BRCA2 genes are in inadequate supply.

"The thought here is that if BRCA1 and BRCA2 are critical gatekeepers of how the heart responds to stressful situations and repairs itself against let's say toxic chemicals, then you're starting with a situation where you have less reserve to fight against those types of situations," Verma said.

If true, the findings are not good news for women with these mutations, who already have the genetic cards stacked against them. It's not uncommon for women with these mutations to have their breasts and ovaries removed as a means of trying to avoid developing cancer.

Verma acknowledge the idea that they may then face an elevated risk of heart disease is difficult. But he suggested there are heart-healthy steps these women can take to lower their individual risk, things like not smoking, drinking in moderation if at all and maintaining a healthy weight.

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