According to a new study in The New England Journal of Medicine, certain patients with T1N0, grade 1 or 2, luminal A breast cancer had a low risk of local recurrence after five years with the omission of radiotherapy.

Whelan TJ, Smith S, Parpia S, et al. Omitting radiotherapy after breast-conserving surgery in luminal a breast cancer. N Engl J Med. 2023;389(7):612-619.

Adjuvant radiotherapy is common in patients who have undergone breast-conserving surgery to reduce the risk of a local recurrence and potentially avoid a mastectomy. However, radiation can cause side effects, including fatigue, skin irritation, breast swelling, pain, induration, and retraction. It can even cause secondary cancers and ischemic cardiac disease, the authors say. 

More so, it’s expensive and inconvenient, typically requiring several weeks of daily treatments.

All of this has led to recent research around omitting radiotherapy, shortening the duration of it, or exploring new irradiation techniques for certain types of breast cancer. 

Shah C, Al-Hilli Z, Vicini F. Advances in breast cancer radiotherapy: implications for current and future practice. JCO Oncol Pract. 2021;17(12):697-706.

Haussmann J, Corradini S, Nestle-Kraemling C, et al. Recent advances in radiotherapy of breast cancer. Radiation Oncology. 2020;15(1):71.

This prospective cohort study, which was funded by the Canadian Cancer Society and the Canadian Breast Cancer Foundation, ultimately included 500 women who were at least 55 years old, who’d had breast-conserving surgery for T1N0 (with node-negative tumors under <2 cm), grade 1 or 2 luminal A–subtype breast cancer, and who’d also received adjuvant endocrine therapy. 

The research team said a Ki67 immunohistochemical analysis was performed centrally and that those patients with a Ki67 index of up to 13.25% did not receive radiotherapy. 

As the authors clarify, grade 1 or 2 luminal A–subtype breast cancer is defined as “estrogen receptor positivity of ≥1%, progesterone receptor positivity of >20%, negative human epidermal growth factor receptor 2, and Ki67 index of ≤13.25%.”

Regarding endocrine therapy, 59% of patients were prescribed an aromatase inhibitor, while 41% were prescribed tamoxifen. Eight patients did not receive endocrine therapy. 82.7% of patients continued receiving endocrine therapy until their last follow-up visit if the visit happened five years or earlier.

Of the 500 enrolled patients, 2.3% (10 patients) had recurrence after five years post-enrollment. In 1.9% of the patients, breast cancer occurred in the contralateral breast, and in 2.7% of patients, recurrence of any type was observed. “Among women who were at least 55 years of age and had T1N0, grade 1 or 2, luminal A breast cancer that were treated with breast-conserving surgery and endocrine therapy alone, the incidence of local recurrence at five years was low with the omission of radiotherapy,” the study concluded. 

“We selected a group of women at low risk on the basis of traditional clinicopathologic factors and a molecular biomarker, and we carefully treated and followed patients prospectively. Our results are generalizable to this group and should not be extrapolated to other groups,” the authors summarized. 

Janie Grumley, MD, breast surgical oncologist and director of the Margie Petersen Breast Center at Providence Saint John’s Center and associate professor of surgery at Saint John’s Cancer Institute in Santa Monica, CA, tells MDLinx that while studies like these are important to determine, ‘who needs what treatment, and when do we need to use it?’ this study was limited in a few key ways. 

“It’s not a randomized, controlled study, which is what we like to do. They just enrolled patients who fit the criteria and treated them, and then calculated risk of occurrence,” Grumley says. “There's value in this, but there's often bias that gets introduced because the people who are signing up may be slightly different from those who wouldn't sign up…This limits applicability to clinical practice,” she says.

Additionally, she questions the five-year follow-up. “A lot of other studies in patients 65 to 70 years old look at 10 years, and we know that favorable cancer doesn't come back in five years—so you need a longer timeframe to answer the question,” Dr. Grumley adds.

Lastly, she says many of her patients say that endocrine therapy is the hardest treatment to endure, so the fact the study’s subjects all had endocrine therapy stood out to her. 

All that being said, she supports researchers addressing the issue of who needs radiation. “For a long time, we told patients that they needed it, but we're doing so many different things now when it comes to breast cancer,” Dr. Grumley says. “Looking for ways to minimize treatment is really important. In medicine, we throw everything and the kitchen sink at cancer, but we may sometimes do more harm than good.”

“Once you sit [patients] down and educate them, they can come up to a good answer around what’s right for them. “

She says every one of her patients is different. “I have patients who will not take endocrine therapy, and I have patients who don't want radiation, so they opt instead for a mastectomy. And other patients think radiation is a piece of cake.”