Researchers Decipher Genetic Combinations That Increase Risk of Breast Cancer in Men

Findings among men differ from those familiar among women, and attest to a difference between the sexes regarding the genetic connection that causes the development of growths in the breast.

An international research team, which included Israeli researchers from the Sheba Medical Center at Tel Hashomer and from Tel Aviv University, reported that it has succeeded in identifying genetic sequences that significantly increase the risk of breast cancer in men. The discovery advances the deciphering of the genetic code for breast cancer in men, which is considered a serious illness that is now diagnosed  mainly in its advanced stages, due to the lack of awareness of it and its problematic image.

In the study, which was published this month in the scientific journal Nature Genetics, the researchers described genetic scans done in six different regions on the genome, in 823 men from England and the United States who suffer from breast cancer. They also carried out parallel scans of 2,795 healthy subjects from a follow-up study taking place in England. An examination of 447,760 genetic sequences indicated the existence of a marker on the gene called RAD51B, whose existence increases the risk of breast cancer in men by 57 percent. In addition, another site was located, called TOX3, in which a change in structure increases the risk of breast cancer in men by 50 percent.

The findings were later confirmed by means of another sampling, which included 438 breast cancer patients and 474 subjects in a control group. The two changes that were diagnosed are unique to breast cancer in men, and are not identified with breast cancer in women – a finding that indicates a possible difference between the two sexes in the genetic connection to the development of cancerous growths in the breast.

Participating in the study were researchers from medical centers in England, Australia, the United States, Denmark, Finland, Italy, Holland, Slovenia, Spain, Sweden and Israel. Also on the staff, which is headed by Dr. Nick Orr of the Institute of Cancer Research in London, is Prof. Anthony Swerdlow, who recently became famous in England after writing a report that downplays the importance of the connection between mobile phones and cancer. Prof. Eitan Friedman, director of the Oncogenetics unit at the Sheba Medical Center, who participated in the study, says that the findings are advancing the discovery of the hereditary tendency for developing breast cancer.

Breast cancer in men is considered a rare illness, and constitutes about 1 percent of all cases of breast cancer, and in Israel about 40 new patients are diagnosed each year. This is an illness that suffers from a problematic image because it is usually accompanied by feelings of embarrassment among the afflicted men. Up until the past decade it was even considered more lethal that breast cancer in women, but today it has been proven that it's the same illness. Although detection of the illness in men usually comes significantly later than in women, which is why the risk of an advanced stage of illness among men is higher. The treatment for breast cancer in men and women is identical, including identical treatment with the drug Tamoxifen, which is administered for five years to reduce the risk of a recurrence of the illness in the other breast.

During the next stage of the project the researchers are planning to examine the genetic sequences surrounding the two sites that were identified in the present study as related to breast cancer in men, in an attempt to identify genetic mutations for which clinical tests can be developed in order to locate them. According to Friedman, "As opposed to a genetic marker, which constitutes a change in the genetic sequence, as identified in the study, our next objective is to identify a genetic mutation, which means an addition or a lack of a basis within the gene that causes the protein created by the gene to be inactive. In future we hope to be able to carry out a clinical test to find genetic mutations of breast cancer in men, but we're not there yet."

The findings join a previous discovery, that a mutation in the gene BRCA2, which is identified with breast cancer in women, is diagnosed among 10 percent of male patients, and also increases the risk of the illness in men. While among women the presence of the mutation increases the risk of breast cancer from 12 percent to 70 percent, among men it increases the risk from less than 0.5 percent to 6 percent throughout their lives.

Among women there are also two additional mutations on gene BRCA1 that increase the risk of breast cancer, which together with the mutation on gene BRCA2 are called "the Ashkenazi mutation," since they appear with higher frequency in Ashkenazi women (of European origin). It was also found in the past, as part of the study of the genetic basis of breast cancer in men, that a woman's risk of contracting cancer if her brother suffers from breast cancer is 30 percent higher than the risk of a woman whose sister suffers from the illness.

Among women medicine has already succeeded, thanks to the identification of the mutations on genes BRCA1 and BRCA2, to enable the birth of children without the gene to mothers who are carriers. This is done by means of a technology of a genetic pre-implantation? diagnosis as part of fertility treatments. Identification of the mutations in women who are carriers also enables a more intensive medical follow-up against breast cancer, including preventive breast removal if necessary.

Today (Monday) marks the beginning of Breast Cancer Awareness Month. During the month famous buildings all over the world will be illuminated in pink, the color that symbolizes the battle against the illness. In Israel 4,000 women are diagnosed with breast cancer every year, and about 1,000 women die of it. One of every eight women is at risk of contracting cancer during her lifetime, up to the age of 90.

A medical procedure at the Hillel Yaffe medical center
Moti Kimchi