Five Questions with Dr. Eileen Connolly: ‘Less is More’ Adage Signifies Shift in Breast Cancer Radiotherapy

October 14, 2020

The field of radiation oncology for treating breast cancer has vastly improved in recent years due to advancements in both technology that has improved radiation treatment delivery, as well as increased understanding of the biology of the disease.

Dr. Eileen Connolly

Dr. Eileen Connolly specializes in breast cancer radiation oncology.

“Improvements in systemic therapy for breast cancer, including regular use of neoadjuvant chemotherapy, targeted HER2 therapies and immunotherapies for triple negative breast cancer has made a huge difference in the breast cancer field as a whole,” says Eileen Connolly, MD, PhD, a radiation oncologist at Columbia University Irving Medical Center and NewYork-Presbyterian Hospital who specializes in breast cancer radiotherapy. “Each advancement in one area of breast cancer therapy affects the other. We—the medical oncologists, the surgeons, and radiation oncologists—work as a multidisciplinary team and our approach is very integrated.”

A physician-scientist, Dr. Connolly is a member of the Herbert Irving Comprehensive Cancer Center and its Tumor Biology and Microenvironment research program, and assistant professor of radiation oncology at Columbia. She also directs a translational research laboratory in the Center for Radiological Research at Columbia, and her research examines the mechanisms of radiation resistance of cancer and studies predictive markers that can help determine a patient’s response to therapy and risk of recurrence.

How has the field of radiation oncology made headway in treating breast cancer?

Radiation therapy for breast cancer is now much more personalized in that we’re both de-escalating treatment and we’re intensifying treatment, depending on the individual patient case. For very low risk breast cancers, we’re giving shorter courses and treating smaller volumes. We are suggesting that some patients can avoid radiation altogether or we can take a more minimalist approach to therapy, such as accelerated partial breast irradiation (APBI). One form of APBI is intraoperative radiation (IORT)— in which radiation is given as a single dose in the operating room—this is something we offer here at Columbia.

On the opposite end, for women who have locally advanced disease we routinely give regional nodal irradiation (RNI), treating not only the breast or post-mastectomy chestwall but also the regional draining lymph nodes—as this has been shown to improve local control and disease free survival. For these patients we are studying how we can refine treatment based on the patient’s response to neoadjuvant chemotherapy (chemotherapy prior to surgery) or the results of genomic testing of their tumor.  We are also investigating if we can shorten the overall course of RNI for locally advanced breast cancer patients to three to four weeks instead of the traditional five- to seven-week course. Shorter “hypofractionated” course of radiation have become standard for node negative disease with most treatments lasting three to four weeks, and in some cases, just five treatments. Finally, for oligometastatic breast cancer patients (those with disease spread to five or fewer sites) we have a national trial investigating if ablation, through stereotactic body radiation therapy (SBRT) and/or surgical resection of all known metastases, will significantly improve overall survival.

Why are oncologists now able to de-escalate therapy?

There are a lot of reasons for this. Breast cancer is now defined by subtype, determined by the expression of estrogen, progesterone, and HER2 receptors on breast cancer cells.  We now understand that some subtypes have a much more favorable prognosis than others. With less risk of local recurrence, this allows us to consider techniques such as APBI or IORT for low-risk disease. The use of neoadjuvant chemotherapy for locally advanced breast cancer has also helped us de-escalate therapy. We now understand that if a patient has a complete pathologic response to chemotherapy they have a better prognosis with lower risk of recurrence. These patients may be able to avoid a mastectomy and axillary lymph node dissection and we are actively studying if we can de-escalate their radiation treatment as well.

How have advancements in genetic testing with respect to breast cancer treatment impacted radiation oncology?
Medical oncologists in breast oncology frequently use genomic tests such as Oncotype Dx or Mammoprint to guide clinical decision, as they help to predict the likelihood of chemotherapy benefit for a patient. There is some data that the Oncotype Dx score may also be predictive of local recurrence risk, and using these results to tailor radiation treatments is an area of investigation. We currently have open TAILOR RT: a national randomized trial of RNI in biomarker low risk node positive breast cancer, which randomizes women with low Oncotype scores to RNI or not. For DCIS (ductal carcinoma in situ), we have a trial ongoing where we are using a test called DCISionRT, which predicts an individual patient’s benefit of radiotherapy following breast conserving therapy. These are very exciting trials and show where we are headed in the future, but we need more data.

What are some of the existing challenges you face as a radiation oncologist?

Unfortunately, there remains a lot of fear and a lack of knowledge in general about radiation therapy. Even in the medical field, if you are not in oncology you don’t really know a lot about radiation, so most people are still afraid of it. It takes a lot of education on our part to really inform patients about the role of radiation in the management of breast cancer as well as reduce the fears patients may have about it. Another challenge we face is that with the increasing use of neoadjuvant chemotherapy, patients who have a complete pathologic response sometime want to avoid radiation altogether. While there are hints that these patients may be able to receive less radiation, we don’t have the data yet to prove that’s the case. Therefore, it is important for patients to meet with us in radiation oncology to discuss their particular case prior to making a decision not to pursue radiation treatment. 

What are some of the key innovations in radiation oncology, say in the last decade, that have greatly benefited breast cancer patients?

We’ve made major strides in the technology of how radiation is delivered.  Compared to a decade ago, everything is now CT-based, or image-based, which allow us to minimize the amount of normal tissue exposed and reduce treatment-related toxicity. We’ve also made simple changes like routinely treating early stage breast cancer patients prone, which is lying on your stomach. It’s using gravity to isolate the breast and allows us to completely avoid heart and lung exposure. Additionally, technologies such as deep inspiration breath hold (DIBH), which is a technique using gaiting on the patient’s breathing, allows us to separate the patient’s heart from the treatment area.  Naturally when you take a deep breath your lungs expand, your heart gets pushed back away from your chest, and that allows us to treat the area with less normal tissue exposure for more locally advanced breast cancer. Finally, volumetric modulated arc therapy (VMAT) is a technique that delivers the radiation dose continuously as the treatment machine rotates. This allows us to shape the radiation delivered to treat our target while minimizing normal tissue exposure for patients receiving RNI.

Those types of innovation from a pure technical machine perspective have made a big advancement in what we are able to do. Then from a biological understanding, the breast cancer field as a whole has made headway with our understanding that different subtypes have different risks, not just for overall survival and disease-free survival but also in terms of local control. Ten years ago it wasn’t widely understood that the risk of local recurrence was greater in triple negative breast cancer compared to hormone receptor positive cancer, for example, and we’re now much more aware of this and will recommend more or less treatment based on this risk. 

The culmination of all of these improvements have made a huge difference in the field.