Editor’s note: This is the first in a two-part series on male breast cancer. Read part two here.
Based on the statistics, Dr. Oliver Bogler couldn’t imagine that his suspicions were true. He’d found a lump in his chest but knew that male breast cancer is “so rare, it’s statistically quite improbable,” he said.
Bogler, a scientist who spent much of his career researching brain tumors, depends on numbers and data. So even as his suspicion of breast cancer began to gnaw, he wondered if it was all in his head.
“I prevaricated several months [after finding the lump],” he said. He’d supported his wife, Dr. Irene Newsham, when she was diagnosed with breast cancer just five years earlier but yet, “I couldn’t think of how to broach the subject with [her].”
In the U.S., “men with breast cancer make up ½ to 1 percent of breast cancer patients,” said Dr. Julie Gralow, a breast cancer researcher at Fred Hutchinson Cancer Research Center and the University of Washington who also treats breast cancer patients at Seattle Cancer Care Alliance. “But even so, several thousand men each year are affected.”
When Bogler, who now leads the teams that support the academic mission of University of Texas MD Anderson Cancer Center, went to the doctor and was diagnosed, at age 46, with stage 3 breast cancer in 2012, he also wasn’t prepared for the dearth of information on the biology of male breast cancer and best treatments for men facing the disease. He decided to take steps to become part of the solution: Bogler embarked on a journey as a cancer patient and clinical trial participant, aiming to provide science more insight into male breast cancer in every way possible.
As Bogler discovered, his course of treatment would be tailored based on insights gleaned from trials conducted on women. Without information based on male patients, oncologists must extrapolate from women, said Gralow.
Knowing which treatments work, and for whom, and how well requires numbers. Many numbers. Many patients, many tissue samples, many clinical records. The scarcity of male breast cancer patients makes it difficult for researchers to amass the numbers they need to begin to understand much about the disease.
Gralow remembers one early, nationwide attempt to study men with breast cancer that she and others in the Southwest Oncology Group conducted. Initiated with high hopes, the trial fizzled as each center struggled to find eligible male patients to enroll — an outcome encountered by many researchers hoping to do strong epidemiological research on men with breast cancer.
“We needed between 50 and 100 men to accrue,” she said, “but we couldn’t get them. [Each center] just got a handful.”
And sometimes, noted Bogler, trials specifically exclude men. “Sometimes it makes sense, and sometimes it doesn’t,” he said.
Small, single center-run trials have provided some clues to the similarities and differences between breast cancer in men and women. As in women, certain mutations in the BRCA2 gene increase risk of breast cancer in men; whether there’s a strong link with mutated BRCA1 is less clear. Conditions that alter the balance between estrogen and testosterone, such as obesity or the possession of an extra X chromosome (called Klinefelter syndrome) also increase risk. And any man who has close relatives diagnosed with breast cancer is also at higher risk of the disease than men without a family history.
Both Bogler, now 49, and his wife, Newsham, are in remission and taking the drug Tamoxifen to try to prevent recurrence of their breast tumors. New clinical trial results suggest that taking the drug for 10 years instead of just five may dramatically improve survival — for women. It is information Newsham and her oncologist can use when deciding whether to extend her treatment. Bogler? He can only guess.
Bogler’s scientific training may have made him unusually aware of how little research has been done on male breast cancer — but it also showed him how to become part of the solution. Now that his treatment, which included chemotherapy, radiation and a mastectomy, has ended, Bogler has made a point of seeking out and joining, when possible, clinical trials. He knows that his initiative can help scientists build a foundation of knowledge that will help men in the future.
Bogler has joined a trial testing an immunotherapy to prevent recurrence and one assessing a therapy for diabetes complications that could help breast cancer patients with nerve pain that lingers after chemotherapy. Bogler has also donated tissue samples to researchers assessing whether genetic testing can point the way to personalized therapy.
The most ambitious study that Bogler participated in was an international, coordinated effort to collect and analyze tissue samples and medical histories of men with breast cancer. He acted as a patient advocate during the study, a role created to help make sure that researchers pursue science with the greatest potential to impact patients. “Although this group is very much focused on the key issues,” he said.
Including almost 1,500 patients diagnosed and treated between 1990 and 2010, the study was designed to solidify insights into characteristics of breast tumors in men, when they’re diagnosed, and how they are treated. Spearheaded by researchers at the European Organization for Research and Treatment of Cancer, the project included a U.S. arm (based at MD Anderson). Fred Hutch’s Dr. Peggy Porter led analysis of tissue samples gathered in the U.S.
What they saw highlighted both similarities and important differences between breast cancer in women and men. As in women, hormone receptor-positive tumors predominated in men — but to a much higher degree. About 70 percent of women with breast cancer have estrogen-positive tumors, but in male breast cancer patients, this number topped 92 percent. But only 77 percent received tamoxifen, the standard treatment for such tumors. Triple-negative breast cancer, which doesn’t express any markers targeted by specific treatments and is very difficult to treat, was much rarer in these men (1 percent, compared to 10 to 15 percent in women).
“This study is a huge step in the right direction,” said Dr. Larissa Korde, a breast cancer researcher and medical oncologist at the University of Washington and SCCA, who was involved in the project. Clarifying the picture of what male breast cancer looks like is just the beginning. Now, researchers have information they need to begin asking other questions — like why are ER-positive tumors so prevalent in men? What are the best treatment strategies for men?
“There are potential differences as to how drugs might act in men and women,” Korde noted. “Tamoxifen is generally effective in hormone receptor-positive tumors in men,” she said, but others, like aromatase inhibitors that may need very low testosterone levels to be maximally effective, might not work as well in men.
The retrospective trial that Korde and Porter participated in was just the first part in a three-part project aimed at finding the answers men need to get the best possible treatment. The international team recently opened a prospective trial that will follow men recently diagnosed with breast cancer. The men enrolled will donate tissue samples and provide information on treatment and response. The network of participating centers will also provide the foundation for the dream of so many researchers: a trial testing the efficacy of a specific breast cancer treatment in men. Again, Bogler will act as patient advocate.
Korde is coordinating enrollment in this trial at SCCA. Again, Porter’s lab is on point to analyze the tissue samples donated in North America. Once the trial is complete and the data analyzed, the team hopes to have new insights into the biology of male breast cancer and how to predict prognosis and best treat men with the disease.
Korde and Gralow are also very interested in the gene mutations that contribute to male breast cancer. Technology is continually advancing, and better ways of uncovering gene mutations may allow researchers to discover links they couldn’t with old methods. High quality tissue samples combined with good clinical data — all of which the new prospective study will provide — will be paramount to answering these questions. These samples, which will be carefully stored, will also make it possible for researchers to “ask questions in five or 10 years we don’t even know yet,” said Gralow.
Bogler is very excited about the new trial. Men enrolled will be followed for up to 10 years afterward—plenty of time to “get good survival data,” he said. As awareness of male breast cancer grows, he’d like to see more research resources devoted to understanding the disease in men: “I’d advocate about 1 percent of the resources go to male-focused studies.”
The above photo of Dr. Oliver Bogler was taken by photographer David Jay as part of The SCAR Project.
Sabrina Richards is a staff writer at Fred Hutchinson Cancer Research Center. She has written about scientific research and the environment for The Scientist and OnEarth Magazine. She has a Ph.D. in immunology from the University of Washington, an M.A. in journalism and an advanced certificate from the Science, Health and Environmental Reporting Program at New York University. Reach her at firstname.lastname@example.org.