Holiday 2004 Newsletter: Radiotherapy for Breast Cancer Patients: Advances in technology and biology improve patient lives

By Dr. Steven J. Chmura
Assistant Professor
Radiation and Cellular Oncology

Radiation therapy of breast cancer patients employs high-energy x-rays or particles (electrons) that directly or indirectly kill cancer cells. Radiation therapy has become an essential component of the multidisciplinary (surgical oncology, hematology oncology, pathology, radiology) treatment of both early and advanced breast cancers. The following essay will outline the advances in radiotherapy both in terms of technology and biology and give guidance as to which patients are more likely to benefit from radiation treatment.

Radiation given to women with breast cancer normally consists of “external beam therapy”. With this type of radiation, a source outside the body is aimed at the entire breast or chest wall to treat areas with known or suspected cancer. In some cases, areas under the shoulder (axilla) and above the collar bone (supraclavicular region) may need to be treated if these areas have a high likelihood of harboring microscopic cancer cells. These radiation treatments are given 5 days/week for 5-6 weeks.

In order to eliminate the need for mastectomy (removal of the breast and lymph nodes) in patients with small breast cancers, surgical removal of the tumor (lumpectomy) is combined with radiotherapy to the entire breast. The whole breast is irradiated because previous studies have shown that small amounts of tumor cells can lie outside the main area of tumor. This is followed by a focused beam (boost) to the small area of the breast where the tumor was felt or seen on mammogram. Numerous randomized studies across the world consistently demonstrated that the need for mastectomy is eliminated by treating patients with lumpectomy and radiation without compromising curability. In fact, recent data suggest that patients undergoing lumpectomy and radiation have a slight improvement in survival compared to those receiving surgery alone.

In the past 30 years we have seen a revolution in the delivery of x-rays as therapy for breast and other cancers. These technologic revolutions have decreased skin reactions resulting in an excellent cosmetic outcome in the hands of a well trained surgeon and radiation oncologist. Furthermore, these technologic improvements may explain the increased cure rates seen in modern groups of both early and advanced breast cancer patients.

At our institution, every breast cancer patient receives “customized” or 3D radiation treatments. Each patient undergoes a planning CT-scan which shows us where the heart, lung, breast, and bones are in relation to the tumor. Using this information along with knowledge of tumor motion, we can employ our sophisticated x-ray delivery machines (linear accelerators) to shape the dose of radiation uniquely for the tumor and individual patient thereby avoiding radiation to some of the heart and lung. This is especially important in women who have received a significant amount of chemotherapy that may already damage those organs. In addition, we employ computerized patient setupprocedures to ensure that each patient is in the correct treatment position each day before radiation is delivered. Soon, these patients will be treated with techniques that synchronize delivery of radiation with each patient’s breathing cycle to further reduce the dose of radiation to these organs.

Over the past 100 years, scientists have discovered that ionizing radiation (IR) kills both normal and tumor cells primarily by damaging the genetic information (DNA) essential to the growth of both tumor and non-tumor tissues. Currently, because there is no effective “monitor” of DNA damage, most patients are treated with the same dose of radiation. This dose was chosen to most likely benefit the largest percentage of patients without causing harm. Yet, despite the technological advances in radiotherapy, little is understood why some patients completing radiation treatments have tumor recur either in the breast or on the chest wall (following mastectomy in advanced cases). However, we do know that the same kind of tumor in different patients exhibits a wide and varied response to radiotherapy. Because of this a minority of patients may be successfully treated with a lower dose of radiation than the standard dose that is currently employed. On the contrary, other patients receiving the standard dose of radiation may be treated with too low of a dose to cure their particular tumor.

While increasing the dose of radiation to the breast or chest wall may improve the probability of tumor cure, this also would increase toxicity to normal tissues such as heart and lung, nearby. Thus, identifying patients most likely to benefit from treatment, and determining whether a curative dose has been delivered to the tumor, could potentially increase the efficacy of radiotherapy and limit toxicity. Our laboratory is currently developing a system to predict not only the response of patients to radiation, but the amount of damage done to both tumor cells and normal cells. We believe that the development of sensitive and specific cellular-level “monitors” of the biological effects of IR will be invaluable clinical tools to both identify breast cancer patients that require higher radiation doses and/or the addition of medicines to augment the effects of radiation, such as chemotherapy or hormonal therapy to optimize clinical outcome. A cellular monitor of IR could also be employed to limit morbidity both in patients who will respond well to radiotherapy and in those who will not benefit from further cytotoxic treatment.

In addition to technological improvements in tumor cell imaging and determining accurate radiation dose, over the next 10 years, we will develop new classes of “targeted” molecules aimed at processes unique to tumor cells. These “small molecules” may represent an entirely new class of chemotherapy that can be combined with radiation to improve patient survival and quality of life. At the University of Chicago these technological and biological advancements discussed here are being not only developed but implemented as quickly as possible for the benefit of our patients.