Breast Cancer in Men Has Distinctive Biological Features

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Breast cancer in men is rare, but it does happen. Less than 1% of all breast cancers occur in men. For men, the lifetime risk of being diagnosed with breast cancer is about 1 in 1,000. Still, some scientists think that the incidence of breast cancer in men is going up.

Researchers have some evidence that breast cancer in men has different biological features than breast cancer in women. Still, because the disease is uncommon, research is limited.

To learn more about the biology of breast cancer in men, researchers compared the Oncotype DX test results of men diagnosed with early-stage, hormone-receptor-positive disease to the results of women diagnosed with the same type of breast cancer. The results found that the breast cancers in men had higher gene expression for:

  • the gene that controls the number of estrogen receptors
  • the gene that controls how quickly the cancer cells divide
  • the gene that controls how quickly the cancer invades healthy tissue

compared to breast cancer in women.

Men also had lower 5-year breast-cancer-specific survival.

The research was published in the May 10, 2018 issue of the Journal of Clinical Oncology. Read the abstract of “Molecular Characterization and Mortality From Breast Cancer in Men.”

The Oncotype DX test is a genomic test that analyzes the activity of a group of 21 genes from a breast cancer tissue sample that can affect how a cancer is likely to behave and respond to treatment.

Doctors use the Oncotype DX test to help figure out a person’s risk of early-stage, estrogen-receptor-positive, HER2-negative breast cancer coming back (recurrence), as well as how likely someone is to benefit from chemotherapy after breast cancer surgery.

The Oncotype DX test results assign a Recurrence Score -- a number between 0 and 100 -- to the early-stage breast cancer. The following ranges are used to interpret the results:

  • Recurrence Score lower than 18: The cancer has a low risk of recurrence. The benefit of chemotherapy is likely to be small and will not outweigh the risks of side effects.
  • Recurrence Score of 18 up to and including 30: The cancer has an intermediate risk of recurrence. It’s unclear whether the benefits of chemotherapy outweigh the risks of side effects.
  • Recurrence Score greater than or equal to 31: The cancer has a high risk of recurrence, and the benefits of chemotherapy are likely to be greater than the risks of side effects.

To do the study, the researchers looked at the Recurrence Scores of 3,806 men and 571,115 women diagnosed with early-stage, estrogen-receptor-positive breast cancer between June 2004 and January 2017.

The researchers noted any differences between men and women:

  • Men were older than women at the time of diagnosis: 64.2 years compared to 59.1 years.
  • Invasive ductal carcinoma was the most common type of breast cancer diagnosed in both genders, but was more common in men: 87.6% compared to 81.3%.
  • Men were much less likely to be diagnosed with lobular breast cancer than women: 1.2% compared to 8.2%.
  • While most of the people in the study had no cancer in their lymph nodes (73.2% of men and 80.1% of women), men were more likely to have one to three lymph nodes involved: 12.1% compared to 8.7%.
  • Overall, the average Recurrence Score in men, 16.8, was similar to the average Recurrence Score in women, 17.0.
  • Most men (58.0%) and women (58.2%) had a Recurrence Score that was less than 18.
  • More men than women had a Recurrence Score that was 31 or higher: 12.4% compared to 7.4%. This difference was statistically significant, which means that it was likely due to the difference in gender and not just because of chance.
  • The tendency of men to have high Recurrence Scores was seen across all age groups, but was most common in men younger than 40.
  • At the same time, very low Recurrence Scores -- scores lower than 11 -- and, specifically, scores of 0, were more common in men than in women, except in men younger than 40.
  • The expression of genes that control the number of estrogen receptors, the rate of cell division, and the ability of the cancer to invade healthy tissue was higher in breast cancers in men than in breast cancers in women.
  • Men had higher rates of larger cancer tumors and grade 3 tumors compared to women.

The researchers had information on survival for 322 men and 55,842 women.

Five-year breast cancer specific survival was:

  • 99.0% for men with a Recurrence Score of less than 18
  • 95.9% for men with a Recurrence Score 18-30
  • 81.0% for men with a Recurrence Score of 31 or higher
  • 99.5% for women with a Recurrence Score of less than 18
  • 98.6% for women with a Recurrence Score 18-30
  • 94.9% for women with a Recurrence Score of 31 or higher

While men and women with Recurrence Scores between 0 and 30 had similar survival rates, women had much better breast cancer survival than men when Recurrence Scores were 31 or higher, even though both men and women in this highest risk group were much more likely to be treated with chemotherapy.

“A larger proportion of men than women had Recurrence Scores greater than or equal to 31, particularly men younger than 40 years of age,” the researchers wrote. “Although a larger proportion of men than women 60 years of age or older had Recurrence Scores of less than 11, including Recurrence Scores of 0, a similar proportion of men and women younger than 40 years of age had very low Recurrence Score results. These observed differences in Recurrence Score distribution suggest that men may have more biologically distinct estrogen-receptor-positive disease subtypes that can be defined by Recurrence Score results: a very low Recurrence Score disease subtype in older men and a high Recurrence Score disease subtype in younger men. BRCA2 mutations, which occur in 4% to 16% of men with breast cancer, may help explain the observed Recurrence Score distribution with age in our study and suggest that BRCA2-associated breast cancer may be a distinct entity in younger men.”

The researchers suggested that future studies should next look at the association between BRCA mutations and Recurrence Score results in men diagnosed with breast cancer.

Because breast cancer in men is rare, it is hard to study the biology of the disease itself, as well as the best way to treat it. Most male breast cancer treatments have been modeled on treatments for women. But as this study shows, breast cancer in men has distinct biological features and treatments need to be tailored to treat them.

If you’re a man who’s been diagnosed with breast cancer, visit the Breastcancer.org Male Breast Cancer pages to learn more about treatments. If you’d like to participate in a clinical trial, visit our Clinical Trials pages to learn more about how these studies are done and how to search for a trial that is best for your unique situation. Also, you can meet other men who have been diagnosed with breast cancer in the Breastcancer.org Male Breast Cancer discussion forum.


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