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What is the recurrence risk in EBC by clinicopathological features?
In real-world studies, the risk of recurrence was higher in EBC patients with high-risk tumors compared to those with nonhigh-risk tumors, highlighting the need for improved treatments in the adjuvant setting for high-risk patients.
Real-World Study in Patients With HR+, HER2- EBC: Risk of Recurrence on Adjuvant Endocrine Therapy
Many patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer (EBC) have a good prognosis but for those with high-risk clinical and pathological characteristics, recurrence can occur in the first few years on adjuvant endocrine therapy (ET). This study investigated risk of recurrence in patients with HR+, HER2- EBC based on clinical and pathological characteristics using data from US oncology practices and examined the need for more effective treatments in patients with a high-risk of recurrence.1
The study was conducted utilizing Flatiron Health electronic healthcare record data and included patients with HR+, HER2- stage IA-IIIC breast cancer, diagnosed January 2011 to March 2020, who received surgery and adjuvant ET.1
Patients were assigned into two groups based on clinical and pathological features.
High-risk group
Patients had the following characteristics:
- ≥4 positive axillary lymph nodes (ALNs), or
- 1-3 positive ALNs and at least one of the following characteristics:
- grade 3
- tumor size ≥5 cm
- Ki-67 ≥20%.1
Nonhigh-risk group
Patients were defined as nonhigh-risk if they did not have the above high-risk characteristics and included a subset with lymph node-negative disease.1
Methods
The Kaplan-Meier method and Cox proportional hazards regression models were used to compare invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) from the initiation of adjuvant ET between the groups using the following sequential gatekeeping strategy: if the differences between the high-risk group of patients and subset of node-negative patients were significant, this allowed the high-risk patient group to be compared to the nonhigh-risk patient group.1
Results
Patients/Demographics
Of the 4028 patients with stage IA-IIIC HR+, HER2- EBC,
- 557 (13.8%) were in the high-risk group, and
- 3471 (86.2%) were in the nonhigh-risk group (including 2867 patients in the node-negative group).1
The median age was 64 years, and patients were predominantly
- female (99.2%)
- white (69.4%), and
- postmenopausal (75.6%).1
Compared with patients in the nonhigh-risk group, the patients in the high-risk group were younger and more likely to be premenopausal, have a breast cancer susceptibility gene mutation, be diagnosed with invasive lobular carcinoma and positive surgical margins, and less likely to have an Eastern Cooperative Oncology Group performance status of 0 or to have received Oncotype DX Breast Recurrence Score testing.1
Follow-up and Treatment
The median follow-up was 39.6 months.1
Of the 557 patients in the high-risk group,
- 231 (41.5%) had ≥4 positive ALNs, and
- 326 (58.5%) had 1-3 positive ALNs with additional risk factor(s) including
- tumor size ≥5 cm (11.7%)
- histological grade 3 (32.0%), and/or
- Ki-67 ≥20% (31.6%).1
Patients in the high-risk group received
- radiotherapy (82.4%), and
- chemotherapy (68.0%).1
The ET first received by patients in the high-risk group included
- aromatase inhibitors (73.9%), and
- tamoxifen (26.0%).1
IDFS and DRFS
Significant differences in IDFS and DRFS were observed between the high-risk group compared to the node-negative group and the low-risk group (log-rank test p<.0001 for all). Results for 2-year IDFS and DRFS rates, as well as comparisons of the high-risk group to the node-negative group and the nonhigh-risk group are summarized in 2-year IDFS and DRFS Rates.
|
High-Risk Group |
Node-Negative Group |
Nonhigh-Risk Group |
2-year IDFS rate, % |
88.1 |
97.4 |
97.1 |
2-year DRFS rate, % |
89.0 |
97.9 |
97.7 |
Abbreviations: IDFS = invasive disease-free survival; DRFS = distant relapse-free survival; HR = hazard ratio.
For patients in the high-risk group, 29.8% experienced recurrence or death by year 5, compared with only 8.0% in the node-negative group and 9.1% in the nonhigh-risk group; similar results were observed for DRFS at year 5.1
Conclusions
Invasive disease recurrence or death within 2 years of initiating adjuvant ET occurred in 11.9% of patients with HR+, HER2- EBC and high-risk clinical and pathologic risk factors; this estimate increased to 29.8% at 5 years. The results from this real-world study suggest that patients in the high-risk group have a risk of recurrence, including incurable metastatic disease, that is more than three-times greater than those in the nonhigh-risk group. To prevent early recurrence and metastases in patients with high-risk HR+, HER2- EBC, optimization of current standard therapies and new treatments are needed.1
Risk of Recurrence by Nodal Status and High-Risk Features in Patients With HR+, HER2-, Early Breast Cancer: An Analysis of Real-world Data
Axillary lymph node involvement is the most significant prognostic marker of recurrence in HR+, HER2- EBC. Most patients with node-positive EBC present with N1 disease but outcomes for N1 disease are variable. The monarchE trial included patients with N1 disease only if they had additional risk features including tumor size ≥5 cm and/or grade 3 disease. This study investigated the real-world risk of recurrence in patients based on nodal status comparing patients who met monarchE clinicopathological features and those did not, as well as patients with N1 disease with and without high-risk clinicopathological features.2
Methods
This study was conducted using Flatiron Health electronic healthcare record data and included patients with HR+, HER2- stage I-III EBC, who had received surgery and adjuvant ET between January 2011 and March 2020. Patients were assigned into groups based on nodal status and the presence of high-risk clinicopathological features such as tumor size ≥5 cm and/or grade 3. The Kaplan-Meier method and Cox proportional hazards regression models were used to compare 5-year IDFS rates between groups.2
Results
The median follow-up period was 42.6 months. The median age of patients with node-positive disease was 60 years and patients were predominantly female. Select patient baseline characteristics are displayed in Patient Demographics and Baseline Characteristics.2
Demographic and Characteristics, % |
High-risk Group |
Non-High-risk Groupa |
||
N1 |
N2/N3 |
N1 |
N0 |
|
Menopausal status |
||||
Premenopausal |
30 |
23 |
19 |
16 |
Perimenopausal |
3 |
2 |
3 |
3 |
Postmenopausal |
61 |
68 |
73 |
77 |
Male |
2 |
<1 |
1 |
1 |
ECOG PSb |
||||
0 |
39 |
33 |
37 |
40 |
1 |
16 |
24 |
17 |
13 |
2+ |
4 |
4 |
3 |
2 |
Pathologic group stagec |
||||
I |
9 |
2 |
24 |
80 |
II |
67 |
7 |
76 |
19 |
III |
24 |
92 |
<1 |
<1 |
Grade |
||||
1 |
4 |
12 |
32 |
33 |
2 |
15 |
54 |
68 |
52 |
3 |
82 |
33 |
0 |
15 |
Tumor staged |
||||
T1 |
27 |
20 |
61 |
78 |
T2 |
46 |
52 |
39 |
19 |
T3 or T4 |
25 |
29 |
0 |
2 |
Abbreviations: ECOG = Eastern Cooperative Oncology Group; PS = performance status.
aNumber includes patients who could not be classified as N0 or N1 (e.g. NX).
bMissing data not excluded: Approximately 40% with missing or unknown data across groups.
cCollected by abstraction from the EHR as explicitly stated by the clinician or pathology report. Therefore, this reflects the staging system (anatomic or prognostic) used by the clinician at the time of diagnosis.
dN1 high-risk 2% with tumor stage of T0.
Invasive disease-free survival rates by nodal status in the high-risk group (HRG) compared to the non-high-risk-group (NHRG) are presented in IDFS in High-risk Group by Nodal Status Versus Non-High-risk Group. Patients in the HRG who had disease characteristics like those in the monarchE cohort 1 had a 3.25-fold higher risk of recurrence than those in the NHRG. Patients in the N1-HRG had a higher risk of recurrence than patients in the N1-NHRG with an absolute difference of 15% at 5 years, and the risk of recurrence in the N1-HRG was 2- to 3-fold higher than in the N0-HRG and N0-NHRG.2
Figure 1 description: At 5 years, invasive disease-free survival rates were 91% for the non-high-risk group, 74% for the N1 high-risk group, 66% for the N2 group, and 65% for the N3 group. Patients in all nodal subgroups are at high risk of recurrence, with at least 2.7-fold increased risk relative to patients without these high-risk features.
Abbreviations: IDFS = invasive disease-free survival; HR = hazard ratio; N1-HR = N1 high-risk; NHRG = non-high-risk group.
Conclusions
In this real-world study, patients with HR+, HER2-, node-positive EBC with clinicopathological features similar to the monarchE cohort 1 population had an increased risk of recurrence compared to patients in the non-high-risk group. Patients in the N1-NHRG had similar recurrence rates to patients with node-negative disease while patients in the N1-HRG had nearly as high risk of recurrence as patients with N2 or N3 disease. These real-world data show that patients with N1 and high-risk features have an increased risk of recurrence compared to patients with N1 disease without high-risk features and support the use of adjuvant abemaciclib plus ET in patients with node positive high-risk EBC.2
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Sheffield KM, Peachey JR, Method M, et al. A real-world US study of recurrence risks using combined clinicopathological features in HR-positive, HER2-negative early breast cancer. Future Oncol. 2022;18(21):2667-2682. https://doi.org/10.2217/fon-2022-0310
2Tolaney SM, Sammons S, Cortes J, et al. Risk of recurrence by nodal status and high-risk features in patients with HR+, HER2-, early breast cancer: an analysis of real-world data. Poster presented at: 47th Annual San Antonio Breast Cancer Symposium (SABCS); December 10-13, 2024; San Antonio, TX. Accessed December 11, 2024. https://sabcs.org/Portals/0/Documents/Full%20Abstracts%20minus%20embargoed_FINAL.pdf?ver=L9oce4fvzC42Ui4sDUmMwQ%3d%3d
Date of Last Review: November 06, 2024