Can breast cancer be treated just as effectively with less radiation? At the Best of Hematology & Breast Cancer 2026 conference, Dr. L. Christine Fang of Swedish Cancer Institute explored how modern de-escalation strategies—ranging from 5-fraction radiation regimens to partial breast irradiation and, in select cases, omission of radiation—are reshaping breast cancer care. Backed by long-term data from landmark trials such as FAST-Forward, IMPORT LOW, and PRIME II, these approaches challenge the long-held belief that more treatment always means better outcomes, instead emphasizing precision, biology, and patient-centered decision-making in early-stage breast cancer.

Dr. L. Christine Fang is a distinguished radiation oncologist at Swedish Cancer Institute, with expertise in treating various cancers, including breast, brain, and lung malignancies. At the Best of Hematology & Breast Cancer 2026 conference in Seattle, Dr. Fang presented a comprehensive overview of de-escalation strategies in breast cancer radiation therapy, challenging the traditional assumption that better cancer control requires more intensive treatment and demonstrating how precision medicine approaches are reshaping radiation oncology practice.

The transcript report below has not been reviewed by the speaker and may contain errors.

The Philosophy of De-Escalation in Breast Cancer Treatment

Traditionally, better cancer control was thought to equate to more intensive treatment. However, de-escalation challenges that assumption by asking what is the minimum treatment needed to achieve the same outcome. The goal is now to prioritize precision over intensity, recognizing that overtreatment can be harmful. The real focus is on patient-centered care.

There are many opportunities for de-escalation throughout the breast cancer treatment continuum, from pre-diagnosis and diagnostics to the actual treatment itself with surgery, radiation, and systemic therapy. Breast cancer treatment has been de-escalating for decades, from mastectomy to breast conservation. The earliest landmark trial was NSABP B-06, which was initiated in 1976—50 years ago—when the field started looking at mastectomy versus lumpectomy specifically. That study compared mastectomy versus lumpectomy alone versus lumpectomy plus radiation, representing one of the earliest attempts to omit radiation.

Reduction in Number of Fractions: Hypofractionation

For de-escalation specifically in radiotherapy, there are a few categories to consider. The first major category is reduction in the number of fractions. In 2010, the 10-year results of the Canadian trial were published in the New England Journal of Medicine, and that was practice-changing. This was moderate hypofractionation, treating patients to the whole breast in 15 or 16 fractions. Multiple other trials looked at essentially the same idea, with one of the bigger ones outside the Canadian trial being the START A and B trials coming out of the UK. These trials normalized the idea that less can be equivalent.

FAST-Forward Trial: Ultra-Hypofractionation

More recently, ultra-hypofractionation trials have been reviewed, starting with FAST-Forward. This was published in 2020 and looked at 4,000 patients with non-metastatic disease. The study compared what is now considered standard hypofractionation with ultra-hypofractionation of 5 fractions. The trial went from 15 fractions down to 5 fractions, examining both 27 Gray and 26 Gray in somewhat of a dose-finding trial.

The 10-year results were just presented at ESTRO 2025. What was published in 2020 showed 5-year outcomes, so there are now 10-year results demonstrating non-inferiority with the 5-fraction regimen. Looking at the figures, the Y-axis goes from 0 to 4, not 0 to 100, so those lines essentially overlap, similar to the figure on the right side. There is really no difference in breast recurrence whether using 5 fractions or 15 fractions, showing feasibility in using 5 fractions.

One concern with larger fraction sizes is cosmesis and patient-reported outcomes. The two things that were worse with 5 fractions were breast induration and breast edema. However, looking at the absolute numbers, they're quite small. Yes, it was double, but it was 1.6% versus 0.8%, with similarly small numbers for breast edema.

Addressing Common Misconceptions About Radiation Dose

A common misconception exists among many patients and even providers within the field regarding total radiation dose. Standard fractionation—which is really no longer standard but was used for decades—involved five weeks of treatment to the whole breast, potentially followed by a boost. That was 50 Gray in 25 fractions, or five weeks of treatment. With moderate hypofractionation adopted 15-20 years ago, treatment moved to 15 or 16 fractions. Most recently, 5-fraction regimens have been studied.

Many people think that going from 25 fractions to 5 means getting a fifth of the radiation, or from 15 to 5 means getting only a third. However, when looking at biologically equivalent doses, it's not just the total dose but also the size of the fraction that matters in the formula. So 50 Gray in standard fractionation remains 50 Gray. The 42.4 Gray delivered in 16 fractions—the most common moderate hypofractionation regimen—is actually biologically equivalent to 47 Gray. When examining 30 Gray in 5 fractions, that's biologically equivalent to 48 Gray, and 26 Gray in 5 fractions equals 40 Gray. It's not nearly the total dose reduction that many people think. This is important to explain to patients during counseling so they're not making decisions based on wrong information.

Reduction in Treatment Volume: Partial Breast Irradiation

The next de-escalation technique is to reduce the treatment volume. This has been a topic of intense development in breast radiation oncology for decades, including interstitial brachytherapy, single-entry catheters (Contura, SAVI, and MammoSite), and intraoperative radiation.

ASTRO Guidelines for Partial Breast Irradiation

The ASTRO guidelines, most recently updated in 2023, provide a framework for appropriate patient selection. The easiest way to think about this is to identify which patients are appropriate and which are inappropriate. Patients appropriate for partial breast irradiation are over age 40—one of the biggest changes over the years, as ASTRO's first consensus statement started at age 60, then lowered to 55, then 50, and now 40. Additional criteria include grade 1 or 2 disease, ER-positive status, and early stage (T1).

Patients not appropriate for partial breast irradiation include women under age 40, those with positive margins for invasive disease, if there's lobular histology with extensive vascular space invasion, HER2-amplified disease where patients are not going to receive HER2-directed therapy.

UK IMPORT LOW Trial

The UK IMPORT LOW trial looked at partial breast irradiation using the same moderate hypofractionation and found non-inferiority, with local recurrence rates being very low. In this case, cosmetics actually improved because using the same fractionation with a smaller volume resulted in less breast firmness than whole-breast treatment.

FLORENCE Trial: Ultra-Hypofractionated Partial Breast

FLORENCE is the ultra-hypofractionated study that came out in 2020, shortly after FAST-Forward, but instead of whole breast, it looked at partial breast. These are women over age 40 with small tumors, comparing standard fractionation of 50 Gray to 30 Gray in 5 fractions. Again, no difference was found—there's no separation of the survival lines.

An example was shown of a patient treated with partial breast radiation in 5 fractions to 30 Gray, demonstrating how much breast tissue is spared when treating only a small volume.

Accelerated Partial Breast Irradiation

Accelerated partial breast irradiation involves treatment over five days but twice daily, seen with BID fractionation using single-entry catheters. However, because the barrier to setting up those programs is much higher, many places began doing this with external beam radiation. The bottom line is this has fallen out of favor because of poor cosmesis. Now that there is data looking at 5 fractions once daily, which is much more convenient, that's really what has replaced twice-daily treatments.

NCCN guidelines fall very much in line with the ASTRO guidelines for partial breast irradiation.

Omission of Radiation Therapy

De-escalation by not giving radiation at all represents the ultimate de-escalation in any therapy. Many studies have looked at this approach. One of the classic studies was CALGB, enrolling patients in the 1990s and looking at the most favorable patients over age 70. PRIME II was more recent, looking at women over age 65, and found that when radiation is omitted, local recurrence goes from 0.9% to 9%. Yes, that is a big difference; however, it is very acceptable to many patients to omit radiation given the low absolute numbers.

More recently, studies are looking more at biology and using genomics. Those studies are ongoing and will provide additional information.

Radiation Alone Versus Radiation Plus Endocrine Therapy

A study from Sweden by Dr. Ashley Morris looked not at leaving out radiation but compared radiation alone to radiation plus endocrine therapy. This was highlighted at San Antonio last month and showed that there really is no significant difference in outcomes in survival or progression-free survival. This is retrospective, so it's not practice-changing, but there is the EUROPA trial ongoing that's looking at endocrine therapy versus radiation therapy alone. That will help elucidate whether radiation alone can be safely offered without endocrine therapy in some of these very favorable patients.

Success Factors and Future Directions

The past, current, and future success of de-escalation is owed to tireless scientists working at the bench as well as improvements across all specialties and disciplines. Improvements in surgery may allow de-escalation in radiation or vice versa, and improvements in systemic therapy contribute as well. The goal is no longer to uniformly apply maximal therapy. The title of these discussions really should not be "doing less" but "doing better," because that is what is truly being accomplished.

Closing Perspective: The Responsibility of Treating Microscopic Disease

The presentation concluded with a story from February 2020, with the emergence of COVID-19 and the first known case in the U.S. having just been reported in Snohomish County. The city and cities across the country implemented shutdown and stay-at-home orders. As first-line healthcare workers, those orders did not apply to medical professionals. Driving into work during those first days of shutdown across the 520 bridge, it was a beautiful clear morning with a lovely view of Lake Washington—lovelier than usual because the bridge was empty, with everyone else at home.

The scene appeared peaceful and beautiful, but in fact, there was a microscopic organism known as the virus that had brought the city and the entire world to its knees. The power of something that could not be seen with the naked eye was profound. This quickly bridged to what radiation oncologists do, particularly breast radiation oncologists, on a daily basis—battling things that cannot be seen but are life-altering. Radiation is directed to regions presumed to potentially harbor microscopic cancer cells.

For all those in the business of adjuvant therapy, treating just the possibility of disease presence and thus also the possibility that disease is not present, there is a special responsibility to do everything possible to best identify the patients who truly benefit from these therapies. That is what really is at the core of de-escalation.