Omitting Radiotherapy after Breast-Conserving Surgery in Luminal A Breast Cancer

Author(s): Timothy J. Whelan, B.M., B.Ch., Sally Smith, M.D., Sameer Parpia, Ph.D., Anthony W. Fyles, M.D., Anita Bane, M.B., Fei-Fei Liu, M.D., Eileen Rakovitch, M.D., Lynn Chang, M.D., Christiaan Stevens, M.D., Julie Bowen, M.D., Sawyna Provencher, M.D., Valerie Théberge, M.D., Anna Marie Mulligan, M.D., Zuzana Kos, M.D., Ph.D., Mohamed A. Akra, M.D., K. David Voduc, M.D., Tarek Hijal, M.D., Ian S. Dayes, M.D., Gregory Pond, Ph.D., James R. Wright, M.D., Torsten O. Nielsen, M.D., Ph.D., and Mark N. Levine, M.D. for the LUMINA Study Investigators*

Source: N Engl J Med 2023; 389:612-619 DOI: 10.1056/NEJMoa2302344

Dr. Maen Hussein's Thoughts

For radiation oncologists: omitting radiation in patients with favorable features of 55 years of age and older.

Additional thoughts from FCS Radiation Oncologist Luis Carrascosa, MD:
This was not a phase 3 randomized trial and there is a lot of controversy regarding newer techniques such as 5-day partial breast irradiation (which I offer at FCS) which is a very good option for women in that age group rather than completely eliminating XRT. Additionally, the real question being investigated, and not addressed in this trial, is noncompliance with aromatase inhibitors and the significant side effects and costs associated with 5 years of endocrine therapy. I would love to have the opportunity to weigh in when we have papers like this.

My take would be: Multidisciplinary approach for breast cancer is recommended. In luminal A breast cancer in women over 55, there is a local control benefit with adjuvant XRT, however it is low. Discussion of shorter radiation schedules such as 5 fraction APBI for women over 55 with luminal A breast cancer is advisable in that subgroup. Encourage patient enrollment/participation in trials of APBI 5 fraction alone vs. 5 years of endocrine therapy alone.

BACKGROUND

Adjuvant radiotherapy is prescribed after breast-conserving surgery to reduce the risk of local recurrence. However, radiotherapy is inconvenient, costly, and associated with both short-term and long-term side effects. Clinicopathologic factors alone are of limited use in the identification of women at low risk for local recurrence in whom radiotherapy can be omitted. Molecularly defined intrinsic subtypes of breast cancer can provide additional prognostic information.

METHODS

We performed a prospective cohort study involving women who were at least 55 years of age, had undergone breast-conserving surgery for T1N0 (tumor size <2 cm and node negative), grade 1 or 2, luminal A–subtype breast cancer (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%), and had received adjuvant endocrine therapy. Patients who met the clinical eligibility criteria were registered, and Ki67 immunohistochemical analysis was performed centrally. Patients with a Ki67 index of 13.25% or less were enrolled and did not receive radiotherapy. The primary outcome was local recurrence in the ipsilateral breast. In consultation with radiation oncologists and patients with breast cancer, we determined that if the upper boundary of the two-sided 90% confidence interval for the cumulative incidence at 5 years was less than 5%, this would represent an acceptable risk of local recurrence at 5 years.

RESULTS

Of 740 registered patients, 500 eligible patients were enrolled. At 5 years after enrollment, recurrence was reported in 2.3% of the patients (90% confidence interval [CI], 1.3 to 3.8; 95% CI, 1.2 to 4.1), a result that met the prespecified boundary. Breast cancer occurred in the contralateral breast in 1.9% of the patients (90% CI, 1.1 to 3.2), and recurrence of any type was observed in 2.7% (90% CI, 1.6 to 4.1).

CONCLUSIONS

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 5 years was low with the omission of radiotherapy. (Funded by the Canadian Cancer Society and the Canadian Breast Cancer Foundation; LUMINA ClinicalTrials.gov number, NCT01791829. opens in new tab.)

Author Affiliations

From the Department of Oncology, McMaster University and the Division of Radiation Oncology, Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, ON (T.J.W., I.S.D., J.R.W.), the Division of Radiation Oncology, Department of Surgery, University of British Columbia and Radiation Therapy Program, BC Cancer Agency, Victoria (S.S.), the Department of Oncology, McMaster University, Hamilton, ON (S. Parpia, G.P., M.N.L.), the Department of Radiation Oncology, University of Toronto, and the Radiation Medicine Program, Princess Margaret Cancer Centre (A.W.F., F.-F.L.), the Department of Pathology, University of Toronto (A.B.), and the Department of Radiation Oncology, University of Toronto and Sunnybrook Odette Cancer Centre (E.R.), Toronto, the Department of Radiation Oncology, University of Ottawa and Ottawa Regional Cancer Centre, Ottawa (L.C.), the Department of Radiation Oncology, University of Toronto and Royal Victoria Regional Health Centre, Barrie, ON (C.S.), the Department of Radiation Oncology, Laurentian University and Radiation Treatment Program, Northeast Cancer Centre, Health Sciences North, Sudbury, ON (J.B.), the Department of Radiation Oncology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC (S. Provencher), the Department of Radiation Oncology, Centre Hospitalier Universitaire de Québec–Université Laval, Quebec, QC (V.T.), the Department of Laboratory Medicine and Pathobiology, and the Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto (A.M.M.), the Department of Pathology and Laboratory Medicine, University of British Columbia, and the BC Cancer Agency, Vancouver (Z.K.), the Department of Radiation Oncology, University of Manitoba and Cancer Care Manitoba, Winnipeg (M.A.A.), the Department of Radiation Oncology, University of British Columbia and Radiation Therapy Program, BC Cancer Agency, Vancouver (K.D.V.), the Department of Radiation Oncology, McGill University, Montreal (T.H.), and the Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver (T.O.N.) — all in Canada.

PACE: A Randomized Phase II Study of Fulvestrant, Palbociclib, and Avelumab After Progression on Cyclin-Dependent Kinase 4/6 Inhibitor and Aromatase Inhibitor for Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor–Negative Metastatic Breast Cancer

Findings from the PACE study show that the addition of Palbociclib to Fulvestrant was not better than Fulvestrant alone, and the addition of Avelumab to Fulvestrant improved and nearly doubled the PFS. This is compelling and should be studied further for our patients with HR+ HER2- MBC.

Ribociclib plus Endocrine Therapy in Early Breast Cancer

For your stage II – III HR+, HER2-neg breast cancer patients. Adjuvant Ribociclib + AI showed a ~3% invasive DFS benefit vs. an AI alone (90 vs 87%). This is a 3-year treatment protocol as opposed to 5 years of an AI, which some patients may appreciate.

Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial

This is a study showing tumor agnostic activity of trastuzumab deruxtecan (T-DXd) with an all-comer overall response rate (ORR) of 37.1%, duration of response (DOR) of 11.3 months and an overall survival (OS) of 13.4 months in an otherwise heavily pre-treated group. Those with IHC-3+ derived larger benefit than 2+. Patients with ERBB2 mutations who had no expression of HER2 were excluded from the trial.

Randomized Trial of Exercise and Nutrition on Chemotherapy Completion and Pathologic Complete Response in Women With Breast Cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis Study

There have been studies showing decreased recurrence in women who underwent curative breast surgeries (walking and yoga). This study assesses if it will affect the intensity of chemotherapy delivered. Although it did not affect it, women who underwent the program had better pathologic complete response (pCR), we need more studies to assess role of nutrition and exercise in treating cancer as we develop a wholesome approach to treat our patients, something we may be able to do in our practice.

Nine-Week Versus One-Year Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: 10-Year Update of the ShortHER Phase III Randomized Trial

This is a 10-year follow-up of the ShortHER study using nine weeks vs. 12 months of adjuvant trastuzumab in HR+ non-metastatic breast cancer. With long-term follow-up, non-inferiority could not be claimed statistically. Still, the DFS/OS results are identical in those patients with N0-N3 disease, while those with N4 disease seemed to have a significant difference favoring 12 months of therapy, suggesting that volume/burden of disease drives the margin of benefit in adjuvant trastuzumab therapy.