Breast-Conserving Surgery with or without Irradiation in Early Breast Cancer

Author(s): Ian H. Kunkler, M.B., B.Chir., Linda J. Williams, Ph.D., Wilma J.L. Jack, M.B., Ch.B., David A. Cameron, M.D., and J. Michael Dixon, M.D.

Source: N Engl J Med 2023; 388:585-594 DOI: 10.1056/NEJMoa2207586

Dr. Maen Hussein's Thoughts

Another radiation trial for older women. Radiation reduces local recurrence but not distant metastasis or overall survival. Again, hope one of our FCS radiation oncologists will share their thoughts in the comment section below.

BACKGROUND

Limited level 1 evidence is available on the omission of radiotherapy after breast-conserving surgery in older women with hormone receptor–positive early breast cancer receiving adjuvant endocrine therapy.

METHODS

We performed a phase 3 randomized trial of the omission of irradiation; the trial population included women 65 years of age or older who had hormone receptor–positive, node-negative, T1 or T2 primary breast cancer (with tumors ≤3 cm in the largest dimension) treated with breast-conserving surgery with clear excision margins and adjuvant endocrine therapy. Patients were randomly assigned to receive whole-breast irradiation (40 to 50 Gy) or no irradiation. The primary end point was local breast cancer recurrence. Regional recurrence, breast cancer–specific survival, distant recurrence as the first event, and overall survival were also assessed.

RESULTS

A total of 1326 women were enrolled; 658 were randomly assigned to receive whole-breast irradiation and 668 to receive no irradiation. The median follow-up was 9.1 years. The cumulative incidence of local breast cancer recurrence within 10 years was 9.5% (95% confidence interval [CI], 6.8 to 12.3) in the no-radiotherapy group and 0.9% (95% CI, 0.1 to 1.7) in the radiotherapy group (hazard ratio, 10.4; 95% CI, 4.1 to 26.1; P<0.001). Although local recurrence was more common in the group that did not receive radiotherapy, the 10-year incidence of distant recurrence as the first event was not higher in the no-radiotherapy group than in the radiotherapy group, at 1.6% (95% CI, 0.4 to 2.8) and 3.0% (95% CI, 1.4 to 4.5), respectively. Overall survival at 10 years was almost identical in the two groups, at 80.8% (95% CI, 77.2 to 84.3) with no radiotherapy and 80.7% (95% CI, 76.9 to 84.3) with radiotherapy. The incidence of regional recurrence and breast cancer–specific survival also did not differ substantially between the two groups.

CONCLUSIONS

Omission of radiotherapy was associated with an increased incidence of local recurrence but had no detrimental effect on distant recurrence as the first event or overall survival among women 65 years of age or older with low-risk, hormone receptor–positive early breast cancer. (Funded by the Chief Scientist Office of the Scottish Government and the Breast Cancer Institute, Western General Hospital, Edinburgh; ISRCTN number, ISRCTN95889329. opens in new tab.)

Author Affiliations

Prof. Kunkler can be contacted at i.kunkler@ed.ac.uk or at the Institute of Genetics and Cancer, University of Edinburgh, Crewe Rd., Edinburgh, EH4 2XR, United Kingdom. A list of the collaborators in the PRIME II trial is provided in the Supplementary Appendix, available at NEJM.org.

HER2CLIMB-05: A Phase III Study of Tucatinib Versus Placebo in Combination With Trastuzumab and Pertuzumab as First-Line Maintenance Therapy for HER2+ Metastatic Breast Cancer

Progression-free survival (PFS) was statistically significantly improved with addition of tucatinib versus placebo 24.9 v 16.3 months regardless of the presence/absence of BM or hormone receptor status.

Role of neoadjuvant versus adjuvant chemotherapy, dose density, and treatment schedule in biologically high-risk HR+/HER2- breast cancer: A pooled analysis of the WSG ADAPT-HR+/HER2- and PlanB trials.

1467 pts with RS > 25 and 551 with clinically (neoadjuvant cohort in ADAPT-HR+/HER2-) or pathologically N2, (longer) docetaxel-based CTx showed better distant, invasive disease-free survival in N2-3 pts patients with RS ≤25, OS was also shown in pts with RS>25 anthracycline regimens did not show a significant survival difference in high-risk HR+/HER2 whether used in neoadjuvant or adjuvant setting. So may be no anthracycline for HR+ve pts who are high risk disease.

The Pathologic Response Evaluation and Detection in Circulating Tumor-DNA Study: Ultrasensitive Circulating Tumor-DNA Assessment of Breast Cancer Minimal Residual Disease

Primary objective not met, ctDNA clearance post- neoadjuvant therapy (NAT) cannot reliably predict pathologic complete response (pCR) and shouldn't be used to defer surgery. But the prognostic data are striking: post-NAT ctDNA positivity independently predicted recurrence in triple-negative breast cancer (TNBC) (HR 8.9), and the postsurgical landmark analysis is essentially binary, 100% of ctDNA-positive patients recurred while 94% of ctDNA-negative patients were disease-free at 5 years (HR 128). Not practice-changing yet pending prospective utility trials, but this strongly validates ultrasensitive ctDNA as a prognostic tool and a smart enrollment biomarker for future escalation/de-escalation trials.

VIKTORIA-1 Trial of Gedatolisib Plus Fulvestrant With or Without Palbociclib in Hormone Receptor–Positive/HER2−/PIK3CA Wild-Type Advanced Breast Cancer

Gedatolisib potently targets all four class I PI3K isoforms and mTORC1 and mTORC2 to comprehensively block the PI3K/AKT/mTOR pathway. PFS was 9.3 m in the gedatolisib-triplet group vs 2.0 m in the fulvestrant group (hazard ratio) HR 0.24, and 7.4 m in the gedatolisib-doublet group HR 0.33 v fulvestrant.

Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer

This is impressive. However, there is no reported placebo trastuzumab deruxtecan arm, so this is not truly a “no chemotherapy” regimen. It is important to remember that deruxtecan is itself a chemotherapy agent. So, this is really comparing deruxtecan vs taxol or more accurately, a comparison of chemotherapy delivery systems.