From: .medpagetoday.com
A new study reports that guideline revisions have introduced a concerning increase in the omission of radiation therapy alone or when combined with estrogen therapy, often leaving older patients vulnerable to preventable locoregional and distant recurrences.
The optimal management of early-stage, hormone receptor-positive (HR-positive) breast cancer in older women remains a clinical challenge. In 2017, the National Comprehensive Cancer Network (NCCN) updated its guidelines to recommend excluding radiation therapy (RT) for women ages 70 years and older with low-risk, stage 1, HR-positive breast cancer who undergo lumpectomy and receive endocrine therapy (ET). While this guideline aimed to minimize unnecessary toxicities and financial burdens, its success depends heavily on long-term patient compliance with ET.
A recent study by Stickland and colleagues, published in Breast Cancer Research and Treatment, took a closer look at the effects of these revised guidelines over a 13-year period.1
“Our goal for this analysis was to analyze practice patterns over time at a single institution to determine whether administered treatments changed after the guidelines were published, as well as to examine associations between delivered treatments and breast cancer recurrence,” the authors stated in their report.1
Characteristics of the study participants
he investigators analyzed a cohort of 383 women ages 65 years and older diagnosed with HR-positive/human epidermal growth factor receptor 2 (HER2)-negative, clinically node-negative breast cancer who underwent breast-conserving surgery between 2012 and 2021.1
Patients diagnosed in 2020 were excluded to avoid confounding treatment patterns caused by the COVID-19 pandemic.
The cohort was highly homogenous, consisting primarily of White, non-Hispanic women (93%). In terms of staging and systemic management, 70% of the women underwent a sentinel lymph node biopsy, whereas only 5.7% required chemotherapy. Patients were followed for a median of 5 years (range 3.1 to 8.0 years).
Across the entire study period, the overall treatment distribution among the cohort was:
- Both ET and RT: 53.0% (n=203)
- ET alone: 28.2% (n=108)
- RT alone: 8.4% (n=32)
- Neither ET nor RT: 10.4% (n=40)
Tracking a range of shifts
Over time, the introduction of the 2017 NCCN guidelines correlated with a shift in treatment choices (P=.01).
- Year of diagnosis
In patients diagnosed in 2012/2013 (n=83):- 67.0% received combined ET/RT
- 13.0% received ET only
- 12.0% received RT only
- 7.2% received neither therapy
- In patients diagnosed from 2019 to 2021 (n=91):
- combined ET/RT dropped to 51.0%
- ET alone increased to 31.0%
- RT alone decreased to 6.7%
- receiving neither therapy increased to 12.0%
- Age at diagnosis
Treatment selection was also strongly associated with age at diagnosis (P<.001).
For women ages 65 to 69 years (n=142):- 75.0% received combined ET/RT
- 13.0% received ET alone
- 9.9% received RT alone
- 2.8% received neither therapy
- For women older than age 80 (n=46):
- 8.7% received combined ET/RT
- 59.0% received ET alone
- 4.3% received RT alone
- 28.0% received neither therapy
- Surgery status
Among the cohort, 70% (n=267) underwent axillary surgery. These women were more likely to receive combined ET/RT (66%; P<.001). Conversely, the 116 patients who didn’t undergo axillary surgery were most likely to receive ET alone (45%), followed by combined therapy (23%), neither treatment (22%), or RT alone (10%).
Rates of endocrine therapy adherence
The recommendation of omitting RT relies on the premise that patients will complete a standard 5-year course of adjuvant ET. However, the study revealed suboptimal compliance across all cohorts.
- Duration by treatment type
- ET alone: 3.45 years (standard deviation [SD] 1.56)
- Combined ET/RT: 3.68 years (SD 1.59)
- Although not statistically significant, patients treated with ET alone demonstrated a trend toward early discontinuation, showing a 23% higher likelihood of stopping treatment before 5 years compared with those receiving combined ET/RT therapy (hazard ratio [HR] 1.23, 95% confidence interval [CI] 0.92 to 1.64; P=.17).
- Duration by year of diagnosis
The average duration of ET has steadily declined over time, dropping from 3.88 years (SD 1.66) in the 2015/2016 cohort to just 3.34 years (SD 1.39) in the 2019 to 2021 cohort.
- Duration by age
ET persistence decreased with advancing age.- 65 to 69 years: 3.68 years (SD 1.64)
- 70 to 80 years: 3.66 years (SD 1.52)
- ≥80 years: 3.01 years (SD 1.60)
No radiation = elevated recurrence risk
The researchers also evaluated recurrence of breast cancer events, including locoregional recurrence, distant recurrence, and new contralateral primary breast cancers. Compared with the reference cohort of patients receiving combined ET/RT, those who omitted components of standard care faced higher risks of disease recurrence.
- Both ET and RT (reference group, n=203)
- locoregional recurrence: 2.0%
- distant metastases: 1.5%
- contralateral disease: 1.0%
- Choosing neither ET nor RT (n=40) was associated with a 10-fold higher risk of recurrence (HR 10.60, 95% CI 4.13 to 27.21).
- locoregional recurrence: 20%
- contralateral disease: 5%
- ET alone (n=108) demonstrated a threefold higher risk of recurrence (HR 3.02, 95% CI 1.28 to 7.16).
- locoregional recurrence: 8%
- distant metastases: 2%
- contralateral disease: 1%
- RT alone (n=32) did not demonstrate a statistically significant increase in recurrence risk.
- locoregional recurrence: 6%
What are the clinical implications?
Following the 2017 NCCN guidelines that support de-escalating RT in older women, the adoption of ET alone, or the complete omission of adjuvant therapy, increased, while the use of RT alone or combined ET/RT therapy declined after lumpectomy. Because the guideline recommendation assumes patients will adhere to a full 5-year ET course, the unexpected rise in patients receiving neither treatment raises concerns for elevated recurrence risks.
Conversely, because modern hypofractionated radiation or accelerated partial breast irradiation protocols offer shorter, logistically easier courses, utilizing RT alone may still serve as a viable alternative for older patients struggling with long-term ET compliance.
Study limitations and next steps
This 13-year, retrospective, single-center study confirms a distinct shift in clinical practice following the publication of NCCN guidelines that support de-escalating RT for small, node-negative, HR-positive/HER2-negative breast cancers.
While providing valuable evidence, several limitations of the study must be considered, including a lack of racial and ethnic diversity among the participants. In addition, the single-center, nonrandomized study design likely introduced bias that influenced treatment choice and, thus, subsequent recurrence rates. And, finally, the overall cohort had favorable low-risk tumor biology, resulting in a low total number of recurrence events, limiting the statistical power of the subgroup analyses.
With the emergence of abbreviated, highly accessible radiation protocols, a short course of RT may offer a more logistically feasible and tolerable alternative to 5 years of daily systemic ET for some older women. Clinicians must carefully weigh these real-world adherence challenges and engage in nuanced, shared decision-making to balance toxicities against the documented risks of disease recurrence. Ongoing trials comparing modern endocrine and radiation regimens are needed to fully understand their impact on disease outcomes and to identify predictors for optimizing patient-specific treatment strategies.
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.