Breast Radiotherapy

Tumors’ response to hormone therapy may be a biomarker for personalization of breast radiotherapy

Posted by

0


How estrogen receptor-positive (ER+) breast cancer responds to hormone therapy may hold keys to understanding how it will respond to radiation therapy, and an experimental drug that increases the effectiveness of hormone therapy also overcomes radiation resistance in breast cancer, a study by UT Southwestern Medical Center researchers shows. The findings of this preclinical study, published in NPJ Precision Oncology, could one day lead to a better approach for personalizing radiation treatments for cancer patients.

Using tumors’ response to a systemic therapy might allow us to personalize radiation treatments in a way that hasn’t been possible before.”

Prasanna Alluri, M.D., Ph.D., study leader, Assistant Professor of Radiation Oncology at UT Southwestern and member of the Harold C. Simmons Comprehensive Cancer Center

ER+ breast cancers are often treated with a systemic therapy such as hormone therapy to shrink tumors, surgery to remove remaining tumors, and finally radiation with or without additional systemic therapy to kill residual microscopic cancer cells. Between 20% and 35% of these cancers show some degree of resistance to hormone therapy.

Doctors can easily learn whether tumors responded to preoperative systemic therapy through imaging. But for radiation therapy, such direct assessment of treatment response is not feasible, Dr. Alluri explained. This results in radiation treatments being administered in a one-size-fits-all fashion, with all patients in a given stage of breast cancer receiving the same intensity and duration of treatment, even though response to radiation can be variable.

Seeking to develop a new approach to predict radiation therapy resistance, Dr. Alluri and his colleagues tested whether there might be a link between the response to hormone and radiation therapies. By introducing mutations in ER+ breast cancer cells that render them resistant to endocrine therapy, the researchers showed that ER+ breast cancer cells that acquired resistance to hormone therapy also exhibited radiation resistance when grown in a laboratory dish.

Similarly, when the researchers implanted hormone therapy-resistant cells into mice, allowing them to develop into tumors, these tumors showed poor response to radiation treatments, again demonstrating a link between response to hormone therapy and radiation therapy.

Earlier research by this team had shown that hormone therapy resistance in ER+ breast cancer tumors is driven by changes in gene expression mediated by a family of proteins known as bromodomains and extraterminal domains (BET). An experimental drug called OTX015 that blocks the function of these proteins reversed hormone therapy resistance. In the current study, Dr. Alluri’s team showed that the BET proteins also play an important role in rendering cells resistant to radiation. Using OTX015, the researchers were able to reverse radiation therapy resistance of hormone therapy-resistant cells grown in a petri dish, as well as hormone therapy-resistant tumors grown in mice.

Dr. Alluri’s team plans to investigate whether the response to other types of systemic drug therapies delivered before surgery for many types of cancers also can be used to predict radiation therapy response – information that could help doctors personalize radiation treatments based on the degree of radiation resistance or sensitivity of a tumor in an individual patient. This approach could advance the field of precision radiation oncology, Dr. Alluri said, where the radiation treatment for each patient is personalized based on individual tumor characteristics.

Other UT Southwestern researchers who contributed to this study include S.M. Udden, GuemHee Baek, Kamal Pandey, Chantal Vidal, Yulun Liu, Asal S. Rahimi, D. Nathan Kim, Chika R. Nwachukwu, and Ram S. Mani.

Dr. Nwachukwu is a Eugene P. Frenkel, M.D. Scholar in Clinical Medicine.

Source:

UT Southwestern Medical Center

Breast Radiotherapy Not Linked to Cardiac Conduction Problems

Posted by

0


Women who undergo breast cancer radiotherapy do not face an increased risk for subsequent heart conduction problems requiring a pacemaker as a result of their treatment, according to new research reported here at the European Society for Radiotherapy and Oncology (ESTRO) 3rd Forum.

“If a woman receives a pacemaker after breast cancer we can assure her it was not due to her therapy,” said study investigator Jens Christian Rehammar, MD, from Odense University Hospital in Denmark.

“Our study is quite unique, as there are no corresponding large studies in breast cancer patients only — previous studies are often mixed with patients with Hodgkin’s lymphoma,” he told Medscape Medical News.
The findings are good news considering recent evidence that an increase in other types of cardiac problems is associated with breast radiotherapy, Dr Rehammar said. He was referring to a 2013 study that found that for every additional gray of radiation to the breast there is 7.4% increase in major coronary events (P < .001) including myocardial infarction, the need for coronary revascularization, and dying from ischemic heart disease ( N Engl J Med. 2013 Mar 14;368(11):987-998).

Analysis of Danish Data

Dr Rehammar’s study merged data from the Danish Breast Cancer Collaborative Group with data from the Danish Pacemaker and ICD Registry to compare women who did and did not receive breast radiotherapy and their likelihood of needing a subsequent pacemaker.

A total of 44,704 women were included in the analysis.

The study found that among 18,308 breast cancer patients who received radiotherapy, 179 (0.98%) received a pacemaker, 90 of whom had been treated for left-sided and 89 for right-sided breast cancers.

For comparison, 1.54% of the nonradiotherapy patients received a pacemaker.

After adjusting for year of treatment, age, and time since breast cancer diagnosis, the risk for cardiac conduction problems requiring a pacemaker was not significantly different between the two groups (relative risk, 1.06; P = .71), he said.
Asked by Medscape Medical News to comment on the findings, Ben Smith, MD, assistant professor of radiation oncology at The University of Texas MD Anderson Cancer Center in Houston, said, “Conduction problems have not really been studied before in breast patients, to my knowledge. I would have predicted this would be a negative study, but it is nice to have data to confirm that.”

Dr Smith, who wrote a recent review of cardiac effects of breast radiotherapy, added, “This study provides reassurance that the typical doses of radiation received by the heart during this era in Denmark did not produce clinically severe damage to the heart’s conduction system. When coupled with prior studies, this body of work suggests that the primary mechanism for cardiac damage following breast cancer radiation is vascular in origin. The conduction apparatus in the heart is fair away from the breast, whereas the blood vessels that feed the heart are closer to the breast.”