Alphonse G. Taghian, MD, Professor at Harvard Medical School and Co-Director of Breast Cancer Research Program at Massachusetts General Hospital, Boston, said that these results from the PRIME II trial are quite similar to those of the older CALGB study first initiated in 1994.1 Both studies had a similar design and similar findings, but the patients in the first study were aged 70 and older, and PRIME II enrolled women aged 65 and older.
Alphonse G. Taghian, MD
“PRIME II confirms exactly what Hughes et al found: In women with tumors up to 3 cm who have a lumpectomy with negative margins, omitting breast irradiation has a 10% recurrence rate at 10 years, whereas radiation plus hormonal therapy has a local failure rate of 1%. This is exactly the same message,” Dr. Taghian said.
“The difference between a 10% rate of local failure compared with 1% could be an important factor for women who are > 65 years old and have a long life expectancy. Omitting breast radiation should not be considered a standard of treatment, but should be considered a treatment option; patients can choose based on the risks and benefits, and that is exactly what I do in my practice,” Dr. Taghian explained.
Weighing the Risks and Benefits
“I tell a patient who is aged > 65 and on hormonal therapy that the risk of local failure is 10% at 10 years. Even though this seems relatively low, the recurrence could have bad emotional and mental consequences on these women and might require more extensive treatment, but with adding radiation upfront, the local failure rate would be 1% or 2%,” Dr. Taghian continued.
“In the past, radiation was too long, too intense, and side effects were many. Sentinel lymph node biopsy was not done in the early 1990s, when the CALGB study was undertaken.
At that time, it made perfect sense to tell patients they could forgo intensive treatment and accept a 10% local failure rate. However, today, with modern radiation techniques, there are great options for much shorter treatment cycles and lower radiation exposure,” Dr. Taghian noted. “Radiation can be completed within 1 week [as with partial-breast irradiation or as in the UK Fast-Forward trials] or once a week for 5 weeks [per the UK FAST trial]. This population of women are much happier coming in once a week for 5 weeks.”
“Hormonal therapy also has side effects, such as joint pain, stiffness, and bone issues, which affect one’s quality of life and compromise compliance, which per some studies is around 50%. Furthermore, some studies suggest that that the magnitude of benefit from hormonal therapy in terms of disease-free survival, for patients with T1 N0 hormonal receptor–positive disease, is quite modest. Putting this all together, it might be a reasonable choice for a patient to opt for radiation therapy, which is well tolerated [with modern techniques] and completed within 5 days with or without the hormonal therapy. Next, we need a study randomly assigning patients to modern radiation therapy alone vs hormonal therapy alone and making radiation alone the tested therapy,” Dr. Taghian proposed. I believe our colleagues from Italy are conducting this important trial.
“Perhaps both approaches might not be needed together to achieve a reasonable outcome. I think the local failure with radiation alone or hormonal therapy alone might be equivalent, although slightly higher than both given together. However, one treatment is completed in 5 days and the other in 5 years; patients should be informed and make the choice . We need to keep moving forward to minimize the intensity of treatment, reduce the risk of local failure, and achieve good quality of life at the same time,” Dr. Taghian stated.
“Breast radiation and hormonal therapy alone should be on the table, and patients should be informed about the potential side effects and benefits of both, alone or combined. The problem is that if you decide to take hormonal therapy and forgo radiation and then after 5 to 6 months find it difficult to take, the window of opportunity for radiation might have passed. However, patients can do 1 week of radiation upfront and then decide to take hormonal therapy; then, they can stop if it affects their quality of life, and they will still have good local tumor control,” Dr. Taghian commented.
“This study is a commendable effort, and it confirms previous data. Omitting breast radiation should not be the standard of care—it should be an option for patients to discuss among other options. A standard of care, by definition, would be superior in a randomized trial. In this trial, omitting radiation led to a 10% local failure rate at 10 years, whereas adding breast radiation led to a 1% rate. Omitting breast radiation may be a good choice for women with comorbidities or patients who live far from a radiation facility,” Dr. Taghian said.
DISCLOSURE: Dr. Taghian reported no conflicts of interest.
1. Hughes KS, Schnaper LA, Bellon JR, et al: Lumpectomy plus tamoxifen with or without radiation in women age 70 years or older with early breast cancer: Long-term follow-up of CALGB 9343. J Clin Oncol 31:2382-2387, 2013.
Omitting postoperative radiotherapy with whole-breast irradiation may not compromise 10-year overall survival or increase the risk of developing metastasis in most women 65 years and older with low-risk breast cancer, according to results of the large randomized PRIME II trial reported at the 2020...