Adjuvant radiation therapy alone improved health-related quality of life (HRQOL) and resulted in fewer treatment-related adverse effects (TRAEs) compared with endocrine therapy alone at 24 months in older patients with stage I hormone receptor–positive, HER2-negative breast cancer, according to findings from the phase 3 EUROPA trial (NCT04134598) presented during the 

Regarding HRQOL, the radiation therapy group had a median QLQ-C30 GHS score of 71.9 (SD, 19.1), and the endocrine therapy group had a baseline median score of 75.5 (SD, 19.3). At 24 months, the radiation therapy group had a mean change from baseline of –1.1 (SD, 18.8) and the endocrine therapy group had a mean change from baseline of –10.0 (SD, 25.8). Adjusted for age and G8 score, the radiation therapy group had a median change of –3.40 (P = .13), and the endocrine therapy group had a median change of –9.79 (P <.0001), both at 24 months.

Additionally, per the QLQ-C30 function scale, the radiation therapy group showed better outcomes in physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning. Per the QLQ-C30 symptom scales, the radiation therapy group had more favorable outcomes for most symptoms including fatigue, nausea and vomiting, pain, dyspnea, insomnia, and appetite loss.

Per the QLQ-BR45 symptoms scale, the radiation therapy group again showed better outcomes compared with the endocrine therapy group, which demonstrated statistically significant worse rates of systemic therapy (P = .047) and skin mucositis symptoms (P = .038).

Survival outcomes in the interim analysis showed that, at 24 months, neither group had any occurrences of ipsilateral breast tumor recurrence (IBTR), locoregional relapse, or breast cancer-related death.

Treatment-related treatment-emergent adverse events (TEAEs) were experienced by 65 patients (67.0%) in the radiation therapy group and 76 patients (85.4%) in the endocrine therapy group (difference, –18.4; 95% CI, –30.2 to –6.2). In each group, 2 patients reported

TEAEs that were fatal: esophageal neoplasia and Listena meningitis in the radiation therapy group and pneumonia and ischemic heart disease in the endocrine therapy group.

The most common TEAEs (occurring in more than 20% of patients) were arthralgia (28.9%), fatigue (33.0%), breast pain (38.1%), and bone pain (23.7%) in the radiation therapy group and arthralgia (69.7%), fatigue (44.9%), hot flashes (32.6%), myalgia (31.5%), bone pain (28.1%), and alopecia (25.8%) in the endocrine therapy group.

Within 24 months, 22.5% of patients who received endocrine therapy switched to a different treatment, and 12.4% of patients discontinued endocrine therapy.

“Radiation therapy or endocrine therapy may be a viable single-modality treatment option, emphasizing the need for a multidisciplinary and patient-centered personalized care,” lead study author Icro Meattini, MD, an associate professor at the Department of Clinical and Experimental Biomedical Sciences “M. Serio” of the University of Florence in Florence, Italy, and coauthors wrote in the presentation.

Primary end points of the study were HRQOL assessed by the global health status scale of the European Organization for Research and Treatment of Cancer at 2 years and the IBTR rate at 5 years. Secondary end points were locoregional recurrence, overall survival, contralateral breast cancer, safety, and HRQOL QLQ-C30/BR45 module domains.

A total of 926 patients were enrolled and randomly assigned, in a 1:1 ratio, and stratified by age (70-79 years vs 80 years or older) and G8 score (14 or lower vs higher than 14) to either the exclusive postoperative radiation therapy group or the exclusive adjuvant endocrine therapy group.

In the radiation therapy group, patients received either whole breast irradiation at 40 Gy in 15 fractions or 26 Gy in 5 fractions via external beam radiation therapy (EBRT) or partial breast irradiation at 26 to 30 Gy in 5 fractions via EBRT; 32 Gy in 8 fractions or 30.3 Gy in 7 fractions via brachytherapy high dose rate; or 0.60-0.80 Gy/hour to 50 Gy via brachytherapy pulsed dose rate. In the endocrine therapy group, patients received aromatase inhibitors or tamoxifen (Soltamox) for 5 to 10 years, per physicians’ choice of treatment.

In this analysis, 207 patients were included (n = 104 in the radiation therapy group and n = 103 in the endocrine therapy group). In the radiation therapy group, 88 patients (84.6%) received partial breast irradiation, and 16 patients (15.4%) received whole breast radiation. The majority of patients were between the ages 70-79 (74.0% in the radiation group and 71.8% in the endocrine group) and had G8 scores higher than 14 (59.6% in the radiation group and 60.2% in the endocrine group).

Patients were 70 years or older and had early luminal-like breast cancer with the following characteristics: HER2-negative, estrogen/progesterone receptor of 10% or more, Ki67 index of 20% or lower, stage pT1ab N0/Nx, any grade or PT1c, grade 1-2.

Meattini M, Carmen De Santis M, Visani L, et al. Exclusive endocrine therapy or radiation therapy in women aged 70+ years with luminal-like early breast cancer (EUROPA): preplanned interim analysis of a randomized phase 3 trial. Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-13; 2024; San Antonio, TX. Abstract GS2-02.

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Risk-reducing mastectomy (RRM) and salpingo-oophorectomy (RRSO) significantly enhance overall survival (OS), disease-free survival (DFS), and breast cancer-free interval (BCFI) in young breast cancer patients with BRCA mutations. The study, involving 5290 patients from 33 countries, revealed that RRM and RRSO reduced risks of DFS, BCFI, and OS events, regardless of BRCA gene, age, tumor subtype, size, and nodal status. These findings underscore the importance of these surgeries in managing cancer risk for young BRCA mutation carriers with early-onset breast cancer.

Radiation therapy produced superior HRQOL outcomes and fewer toxicities vs endocrine therapy in older patients with stage I luminal-like breast cancer.

Postoperative Radiation Therapy Improves HRQOL, Safety in Early-Stage HR+/HER2– Breast Cancer

Findings from an international, retrospective cohort study showed that risk-reducing mastectomy (RRM) and/or risk-reducing salpingo-oophorectomy (RRSO) were associated with improved overall survival (OS), disease-free survival (DFS), and breast cancer–free interval (BCFI) in patients 40 years of age or younger with breast cancer and a germline 

At the median follow-up of 8.2 years (IQR, 4.7-12.8), 691 (13.0%) OS, 1928 (36.3%) DFS, and 1753 (33.0%) BCFI events were recorded.

For patients who experienced RRM, there was a notably reduced risk of DFS (adjusted HR [aHR], 0.58; 95% CI, 0.52-0.65) and BCFI (aHR, 0.55; 95% CI, 0.48-0.62) events, irrespective of 

gene, age at diagnosis, tumor subtype, tumor size, and nodal status. OS events were also noted (aHR, 0.65; 95% CI, 0.53-0.78).

At the time of RRM, the median age was 36.6 years (IQR, 33.0-39.6); the median time from diagnosis to RRM was 0.8 years (IQR, 0.5-2.7); median follow-up after RRM was 5.1 years (IQR, 2.7-8.3). Per the sensitivity analyses, only patients tested for 

before or at diagnosis were included (aHR, 0.61; 95% CI, 0.42-0.88), as well as those with delayed entry (aHR, 0.54; 95% CI, 0.44-0.66), and when the 3-year landmark analysis was performed (aHR, 0.57; 95% CI, 0.45-0.71).

For patients who experienced RRSO, there was a significant reduction in risk of BCFI (aHR, 0.65; 95% CI, 0.57-0.74) and DFS (aHR, 0.68; 95% CI, 0.61-0.77) events. There was also reduced risk of OS (aHR, 0.58; 95% CI, 0.47-0.70) events in this group, irrespective of age at diagnosis, tumor size, and nodal status. There was significant interaction with regards to tumor subtype (triple-negative breast cancer [TNBC]: aHR, 0.43; 95% CI, 0.32-0.58; hormone receptor–positive breast cancer: aHR, 0.80; 95% CI, 0.61-1.06) and specific to 

At the time of RRSO, the median age was 39.7 years (IQR, 37.4-41.8); the median time from diagnosis to RRSO was 3.0 years (IQR, 1.3-6.8); the median follow-up after RRSO was 4.9 years (IQR, 2.3-8.1). Per the sensitivity analysis, only patients tested for 

before or at diagnosis were included (aHR, 0.70; 95% CI, 0.49-1.01), when delayed entry was accounted for (aHR, 0.47; 95% CI, 0.38-0.58), and when the 3-year landmark analysis was performed (aHR, 0.58; 95% CI, 0.47-0.72).

“Our results showed that undergoing RRM and/or RRSO was associated with improved OS, DFS, and BCFI in this special clinical setting,” Matteo Lambertini, MD, PhD, associate professor and consultant in medical oncology at the University of Genova – IRCCS Policlinico San Martino Hospital in Genova, Italy, wrote in the presentation.

 “These findings may help to improve the counseling on cancer-risk management strategies for 

carriers with young-onset breast cancer but should not be used to counsel 

carriers with a diagnosis of breast cancer at an older age.”

Patients from 33 countries were included in the study; 6238 patients were registered for participation, and 5290 were included in the final retrospective study. Analysis was split between patients who did (n = 2910) or did not (n = 2380) undergo RRM and patients who did (n = 2782) or did not (n = 2508) undergo RRSO.

The median age at diagnosis was 35.0 (IQR, 31.0-38.0): 1105 patients (20.9%) were 30 years of age or younger, 1929 patients (36.5%) were between 31 and 35 years, and 2256 patients (42.6%) were between 36 and 40 years.

Regarding genes, 3361 patients (63.5%) had the 

gene. Of them, 2581 patients (48.8%) were tested for 

Of note, 2708 patients (51.2%) had N0 nodal status; 1898 patients (35.9%) and 2596 patients (49.1%) had luminal-like tumors and TNBC tumors, respectively. A total of 4860 patients (91.8%) had undergone chemotherapy.

Patients were required to have stage I to III invasive breast cancer, a diagnosis between January 2000 and December 2020, be less than 40 years of age at diagnosis, and have known germline-likely pathogenic/pathogenic variants in 

Patients were excluded if they had stage IV de novo breast cancer, a history of ovarian cancer or other malignancies without prior breast cancer, were 

healthy carriers, or had no information on uptake/timing of RRM and/or RRSO, or uptake before their breast cancer diagnosis.

“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young 

 mutation carriers with a prior history of early-onset breast cancer,” Lambertini said.

 “We believe that our findings are critical for improving the counseling of 

 mutation carriers with early onset breast cancer on cancer-risk management strategies.”

Lambertini M, Sonnenblick A, Agostinetto E, et al., Association between risk-reducing surgeries and survival in young BRCA carriers with breast cancer: results from an international cohort study. Presented at the 2024 San Antonio Breast Cancer Symposium; December 10-13, 2024; San Antonio, TX. GS1-08.

BRCA-mutation carriers with a history of early-onset breast cancer may benefit from risk-reducing surgery. News release. American Association for Cancer Research. December 11, 2024. Accessed December 11, 2024. https://tinyurl.com/3bkmzb3r

Risk-reducing surgery improved survival outcomes in younger patients with breast cancer and a germline BRCA mutation.

Tim Cortese

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Postoperative Radiation Therapy Improves HRQOL, Safety in Early-Stage HR+/HER2– Breast Cancer

Risk-Reducing Surgery Improves Survival Outcomes in Younger BRCA+ Breast Cancer