More women in the United States are surviving and thriving after breast cancer than ever before. In fact, in the last 30 years, the breast cancer death rate has dropped an astounding 40%. The decreases are believed to be the result of finding breast cancer earlier through screening, increased awareness, and better treatments.
Still, the American Cancer Society estimates 268,600 women and 2,670 men will be diagnosed with invasive breast cancer in 2019. This is why research into every aspect of breast cancer continues, including ways to help prevent it, find it when it can be treated most effectively, treat it with fewer side effects, reduce the chances of recurrence, and improve the quality of life after breast cancer treatment.
This research is happening on a variety of levels. There’s the traditional work in labs with cells or mice and clinical trials with patients. Research outside the lab can also lead to significant improvements, such as studying specific communications between people and their health insurance company, health care professional, or health care provider, or by learning about the obstacles that keep people from being able to access care that’s been found to be the most effective.
Here’s how 3 scientists awarded grants from the American Cancer Society are contributing to research that may help the families affected by breast cancer in the future.
Women with dense breasts have a high percentage of fibrous, less fatty breast tissue, which can make it harder to see cancer on mammograms. Women with dense breasts have a higher risk of developing breast cancer compared to women with average breast density.
Nancy Kressin, PhD, wants to educate women about the risks associated with having dense breasts. As a senior research career scientist at the VA Boston Healthcare System, Kressin is studying whether mammography results sent to women and their doctors (1) clearly state that having dense breasts increases the risk for developing breast cancer, and (2) specifically advise what women with dense breasts can do to lower their risks.
Nancy Kressin, PhD
The goal of our research is to find the right words and level of information to include in dense breast notifications after a mammogram to help women understand how their breast density affects their risk for breast cancer and whether extra screening is right for them."
Most states now have laws that require health care facilities to inform patients when their mammography finds the presence of dense breast tissue. Until now, each state has set its own laws about what information a woman with dense breast tissue and her doctor are told in a mammography report. For instance, some states haven’t required that a woman be told about her breast density. Recently the US Food and Drug Administration (FDA) proposed a minimum standard and specific language for dense-breast notification (DBN), adding consistency to letters about the results of a screening mammogram from facilities across the US.
Kressin and her research team want to make sure these letters have the effect they’re designed for. “We gave the FDA input when they were accepting public comments, and we plan to share the results of our study about the effects of DBNs with them,” she said.
Her study involves surveying 2,000 women ages 40 to 74 who had a screening mammogram within the last 2 years and who don’t have a history of breast cancer. Kressin and her research team plan to talk with women in states that have DBNs in place and states that don’t. She wants to find out what level of awareness and knowledge women have about their own breast density, and how it affects their future plans to get screened for breast cancer.
“The intent of the DBNs is to encourage women to go the doctor and discuss their personal risk and whether they would benefit from additional screenings,” said Kressin. “We will be asking women if they are talking to their doctor, whether they plan to be screened with another method, and whether they feel informed, anxious, or confused by the information.”
Her team will also assess whether a woman’s race, ethnicity, and socioeconomic status affects her response to the DBN. “In many states, we have found the reading level of the notifications is higher than the average literacy level of women in the state, and that may just cause confusion.” she said.
“If the notification makes women feel more engaged and informed, that’s a good thing. But if women feel so unclear about what to do that they decide to do nothing at all, that’s a problem.” The goal of their research, Kressin said, is to find the right words and level of information to help women understand how their breast density affects their risk for breast cancer and whether extra screening is right for them.
“When breast cancer is only in the breast, it’s quite treatable. But in some women, as many as 10 or 20 years after treatment, the breast cancer comes back in a different part of the body, often the brain, liver, lung, or bone. Unfortunately, these recurrent tumors are much harder to treat and more deadly than the original tumor,” said James Alvarez, PhD.
James Alvarez, PhD
“The imaging methods we currently have, like mammography and PET scans, don’t let us see dormant cells in women with breast cancer, so studying them in patients is very challenging. That's one reason we work with mice."
He's studying recurrent breast cancer in mice at Duke Cancer Institute in Durham, North Carolina, to better understand what makes a cancer cell that’s been dormant—not growing—suddenly reactivate.
It’s believed that this regrowth happens because at some point a few treatment-resistant cancer cells broke away from the original tumor and migrated via the bloodstream to a part of the body far from the breast. The cells may stay there, not growing for many years, in a state of dormancy.
“The imaging methods we currently have, like mammography and PET scans, don’t let us see dormant cells in women with breast cancer,” Alvarez said, “so studying them in patients is very challenging.” By working with mice, he’s determined that about 50% of these new tumors are made up of cells that are no different from the cells in the original tumors. “That means there are no genetic differences in the cells—the DNA of the cancer cells are the same,” Alvarez said. But there could be epigenetic changes, meaning there are differences in which genes are turned on and off.
Genes are made up of long strands of DNA, and certain proteins “hug” the DNA to condense it to its tiny size. If those proteins wrap the DNA too tightly, that gene is turned off.
His team found that in dormant breast cancer cells, the protein G9a is required for the cells to survive. G9a may turn off genes that are responsible for controlling the body’s inflammatory response. An uncontrolled inflammatory response may be a critical factor in whether a new tumor forms.
“In some of our earlier studies with mice, we found that a drug that blocks the protein G9a (called a G9a inhibitor) completely wiped out the reactivated tumor cells but had no effect on the primary tumor cells or on normal cells,” Alvarez said. “So, we know there is something very unique about the recurrent tumor cells that makes them sensitive to G9a.”
In his new study, Alvarez and his team are using mice and tissue samples from people with breast cancer. Their key questions are: What makes these cells start growing again after they’ve spent so many years inactive, and how can we keep them permanently inactive? Specifically, they want to find out:
While this research is promising, Alvarez pointed out that it doesn’t solve all problems with breast cancer recurring. “We think this G9a inhibitor will only be effective in recurrent tumors where there is not a new genetic mutation,” he explained. “There are many ways the cancer cells from a first tumor can turn into a new tumor in another part of the body, and we’re hopeful that a drug targeting G9a might block at least one of those ways.”
Exercise can have profound benefits for breast cancer survivors, Christina Dieli-Conwright, PhD, said. “It may help them lose weight and feel stronger, reduce depression and improve quality of life, and lower the risk of co-morbidities, including heart disease and diabetes.” She's the director of the Integrative Center for Oncology Research in Exercise at the City of Hope National Medical Center in Duarte, California.
Christina Dieli-Conwright, PhD
Our clinical trial is an exercise program designed specifically to help Latinas who've had breast cancer overcome obstacles to exercising regularly. We integrate bilingual staff throughout all patient interactions, and all staff members go through cultural sensitivity training."
Dieli-Conwright wants to help reduce disparities experienced by the Latina community by helping breast cancer survivors overcome barriers to exercising regularly.
“Based on our previous work, we’ve found the biggest barriers to exercise in the Latina community are family commitments. Women are often taking care of their children, grandchildren, parents, cousins, or siblings, and they don’t have the same flexibility of time. They also have work obligations and transportation concerns,” she said.
In order to find the best way to encourage Latina breast cancer survivors to use exercise as a tool to reduce co-morbidities and improve their fitness level and quality of life, Dieli-Conwright is using her American Cancer Society grant to enroll 160 women in a 12-month exercise program called the ROSA Trial: Reducing Metabolic Dysregulation in Obese Latina Breast Cancer Survivors.
The program is designed specifically for Latinas. “We integrate bilingual staff throughout all patient interactions, and all staff members go through cultural sensitivity training,” Dieli-Conwright said.
Half the participants will be randomly assigned to the progressive combined aerobic and resistance training (PCT) group. The other half will receive usual care (UC). The study consists of 3 phases. At the end of each phase, researchers will take body scans, assess fitness levels, and take blood samples to measure insulin resistance.
The UC group will be asked to maintain their current activity level for all 3 phases and will serve as the comparison group. After the 12-month study, they’ll be offered the PCT program.
In phase 1, clinical trial participants in the PCT group will participate in a 4-month supervised exercise program that includes American Cancer Society recommendations for 150 minutes of aerobic exercise and 2 sessions of resistance training per week. Participants will meet 1 to 1 with a personal trainer 3 times a week in the exercise research facility at the City of Hope National Medical Center. They’ll also be offered multiple transportation options.
In phase 2, women in the PCT group will be offered a 4-month family membership at the YMCA of their choice. The goal is to encourage continuation of an exercise routine in a community setting, but without the supervision of a trainer. The YMCA will offer child care.
In phase 3, study participants in the PCT group will be asked to continue to exercise on their own without any supervision and without the resources of the YMCA or any other facility.
Dieli-Conwright hopes the women’s experiences in a culturally sensitive, de-la-clinica-a-la-communidad (Spanish translation of “from-the-clinic-to-the-community”) program will inspire life-style changes in which the women continue to incorporate exercise into their routines, leading to fewer co-morbidities and better quality of life.
“Our goal is to develop an exercise model that can be adapted across other groups of breast cancer survivors and survivors of other types of cancer,” she said.