The study examined patient and tumour factors that influence the receipt of breast surgery in older women with ER-positive and ER-negative operable breast cancer in England and Wales. 83,188 women were identified through linked cancer registration and routine hospital datasets. The analysis found that fewer fit older women receive surgery if diagnosed with ER-positive compared to ER-negative EIBC.
Abstract
Background
Studies reporting lower rates of surgery for older women with early invasive breast cancer have focused on women with oestrogen receptor (ER)-positive tumours. This study examined the factors that influence receipt of breast surgery in older women with ER-positive and ER-negative early invasive breast cancer .
Methods
Women aged 50 years or above with unilateral stage 1–3A early invasive breast cancer diagnosed in 2014–2017 were identified from linked English and Welsh cancer registration and routine hospital data sets. Logistic regression analysis was used to evaluate the influence of tumour and patient factors on receipt of surgery.
Results
Among 83 188 women, 86.8 per cent had ER-positive and 13.2 per cent had ER-negative early invasive breast cancer. These proportions were unaffected by age at diagnosis. Compared with women with ER-negative breast cancer, a higher proportion of women with ER-positive breast cancer presented with low risk tumour characteristics: G1 (20.0 versus 1.5 per cent), T1 (60.8 versus 44.2 per cent) and N0 (73.9 versus 68.8 per cent). The proportions of women with any recorded co-morbidity (13.7 versus 14.3 per cent) or degree of frailty (25 versus 25.8 per cent) were similar among women with ER-positive and ER-negative disease respectively. In women with ER-positive early invasive breast cancer aged 70–74, 75–79 and 80 years or above, the rate of no surgery was 5.6, 11.0 and 41.9 per cent respectively. Among women with ER-negative early invasive breast cancer, the corresponding rates were 3.8, 3.7 and 12.3 per cent. The relatively lower rate of surgery for ER-positive breast cancer persisted in women with good fitness.
Conclusion
The reasons for the observer differences should be further explored to ensure consistency in treatment decisions.
Resumen
Antecedentes
Los estudios que publican una tasa menor de cirugía en las mujeres mayores con cáncer de mama invasivo precoz se han centrado en mujeres con tumores positivos para receptores de estrógeno (estrogen receptor ER). Este trabajó analizó los factores que influyen en la realización de cirugía de mama en mujeres mayores con cáncer de mama invasivo precoz ER positivo y ER negativo.
Métodos
A partir del registro de cáncer inglés y galés y de las bases de datos hospitalarias se identificaron las mujeres de ≥ 50 años con cáncer de mama invasivo precoz unilateral en estadios 1-3A diagnosticados entre 2014-2017. Se utilizó una regresión logística para evaluar la influencia del tumor y los factores de la paciente en la práctica de la cirugía.
Resultados
De 83.188 mujeres con cáncer de mama invasivo precoz, el 87% tenía ER positivo y un 13% ER negativo. Este porcentaje no se vio afectado por la edad en el momento del diagnóstico. En comparación con las mujeres con cáncer de mama ER negativo, las mujeres con cáncer de mama ER positivo tuvieron tumores de bajo riesgo: G1 (20% versus 2%), T1 (61% versus 44%) y N0 (74% versus 69%). Los porcentajes de mujeres con alguna comorbilidad (14% versus 14%) o con algún grado de fragilidad (25% versus 26%) fueron similares entre las mujeres con ER positivo y ER negativo, respectivamente. La tasa de no realización de cirugía fue del 6%, 11% y 42% en las mujeres con cáncer de mama invasivo precoz ER positivo de 70 a 74 años, 75 a 79 años y ≥ 80 años, respectivamente. Estas tasas fueron del 4%, 4% y 12% en las mujeres con cáncer de mama invasivo precoz ER negativo. La tasa relativamente más baja de cirugía para el cáncer de mama ER positivo persistió en mujeres con buen estado físico.
Conclusión
En Inglaterra y Gales, la indicación de cirugía en pacientes mayores sin contraindicación quirúrgica es menor en los carcinomas de mama precoz invasivos ER positivo en comparación con los ER negativo. Deben analizarse las razones de estas diferencias para garantizar una coherencia en las decisiones del tratamiento en las mujeres mayores.
Introduction
Oestrogen is the main hormonal regulator for modulating the growth, differentiation and function of breast tissue. Invasive breast cancer is often described by its oestrogen receptor (ER) status, which is either positive, based on the presence, or negative, based on the very low presence or complete absence, of receptors to oestrogen. Up to 80 per cent of women with early invasive breast cancer have ER-positive tumours, and these women have a better prognosis than women with ER-negative breast cancer1.
Surgery is recommended as standard of care for women with early invasive breast cancer, irrespective of ER status2. UK population-level studies consistently report a lower rate of surgery in older women compared with their younger counterparts3–6. This pattern has been particularly apparent in older women with ER-positive early invasive breast cancer. Recent findings by the National Audit of Breast Cancer in Older Patients (NABCOP) are of a higher rate of surgery in women aged 70 years or above with ER-negative early invasive breast cancer than in women of similar age with ER-positive disease7. There was also less variation in the rate of surgery for older women with ER-negative early invasive breast cancer across National Health Service (NHS) organizations in England and Wales7,8.
A key difference in the treatment of women with ER-positive and ER-negative early invasive breast cancer is the option of primary endocrine therapy for women with ER-positive breast cancer and poor fitness/life expectancy2,9. Outcomes of primary endocrine therapy are inferior to those for surgery10,11, and it is therefore not an equally effective primary treatment alternative for early invasive breast cancer. For women with ER-negative disease, there is no alternative systemic treatment equivalent to primary endocrine therapy, and clinical guidelines offer no recommendations on how treatment should be modified in patients with poor fitness9.
This study aimed to investigate the relationship between tumour and patient factors on the likelihood of not receiving surgery in women aged 50 years or above with ER-positive and ER-negative early invasive breast cancer.
Methods
This population-level cohort study was undertaken as part of the NABCOP. The NABCOP uses pseudonymized patient-level data sets provided by the National Cancer Registration and Analysis Service in England and by the Wales Cancer Network in Wales. The data sets included national cancer registrations and extracts from the routine hospital admission databases for NHS hospitals, the English Hospital Episode Statistics (HES) and the Patient Episode Database for Wales (PEDW). Survival information is recorded in the Civil Registration/Mortality data. Full details of the NABCOP cohort are described in the 2019 annual report7.
The study was exempt from UK National Research Ethics Committee approval as it involved secondary analysis of an existing data set of anonymized data. The NABCOP has approval for processing healthcare information under Section 251 (reference number 16/CAG/0079) for all NHS patients aged 50 years and over diagnosed with breast cancer in England and Wales.
Study population and definitions
The study included women aged at least 50 years, newly diagnosed with unilateral early-stage (UICC TNM staging classification, seventh edition12 stage 1–3A) invasive breast cancer (ICD-10 code C50) from 1 January 2014 to 31 December 2017 in England and Wales. Among the 109 018 eligible women in the NABCOP data sets, those with a missing record of ER status (10 951 women, 10.0 per cent) or other key study variables (14 927, 13.7 per cent), or who were borderline in ER status (42), were excluded.
Information on patient demographics (age, social deprivation), date of diagnosis, method of presentation and tumour characteristics was obtained from the national cancer registration data set. Social deprivation was measured using the Index of Multiple Deprivation (IMD), with IMD values for geographical areas in England13 and Wales14 converted to quintiles. Patient fitness was assessed using co-morbidity and frailty measures. Co-morbidity burden was measured using the Royal College of Surgeons of England modified Charlson Co-morbidity Index (CCI)15, excluding malignancy16. This index is calculated based on the presence of specific medical problems, identified using the ICD-10 diagnostic information in HES and PEDW up to 2 years before the date of cancer diagnosis. The study also used a measure of frailty, a concept distinct from co-morbidity that describes age-related decline in physiological reserve and increased vulnerability to stressors17. Frailty was measured using the secondary care administrative records frailty (SCARF) index18, which shares a similar construct of frailty deficits to the electronic Frailty Index19, for use in routine hospital databases. The SCARF index is calculated from 32 frailty deficits, identified using the ICD-10 diagnosis codes within hospital admission records in HES/PEDW, up to 2 years before the date of diagnosis18.
Outcomes
Surgery was defined by the first type of breast surgical resection recorded in HES and PEDW during the 12 months after the date of diagnosis, to allow for the use of any neoadjuvant therapy. Both HES and PEDW capture surgical procedures using Office of Population Censuses and Surveys (OPCS) codes, with the code B28 (excluding B28.4 and B28.6) defining breast-conserving surgery (BCS) and the code B27 defining mastectomy.
The study also examined a number of short-term outcomes associated with surgical safety: the duration of inpatient hospital stay (defined as the number of days from date of surgery to discharge), 30-day postoperative mortality, and 30-day emergency readmission rates after discharge.
Statistical analysis
The proportion of patients not receiving surgery was calculated for women with ER-positive and ER-negative early invasive breast cancer, and among groups with different patient and tumour characteristics. The statistical significance of differences between the groups was assessed using the statistical tests appropriate for continuous (t-test) or categorical (chi-square test) variables. Patient and tumour factors of interest included age, deprivation quintile, CCI, SCARF index, tumour grade, tumour size (T category), the presence of malignant lymph nodes (N category), human epidermal growth factor receptor (HER) 2 status, and mode of presentation (screen-detected or symptomatic). Short-term surgical outcomes were also determined for women aged 50–69 or 70 years and above with ER-positive and ER-negative disease.
Multivariable logistic regression was used to investigate how all the patient and tumour factors were associated with the likelihood of no surgery. Age was included in the model as a continuous variable, and a cubic spline was used to accommodate its non-linear effect20. The spline knots were defined at ages 51, 73, 85 and 90 years, which were selected based on the Akaike information criterion. The model also included interaction terms to capture differences in the patterns of surgery between women with ER-positive and ER-negative early invasive breast cancer. The interaction terms were ER status and age, ER status and N category, and ER status and frailty. Performance of the model was evaluated in terms of its calibration and discrimination21 in the overall cohort and within the two ER subgroups.
As the spline coefficients and the interaction terms are difficult to interpret, predictions from the model were produced to illustrate the relationship between age and the likelihood of no surgery for women with ER-positive and ER-negative early invasive breast cancer22. The predictions were produced for four patient subgroups: women with low-risk (grade 1, stage T1 N0) or high-risk (grade 3, stage T2 N1) breast cancer, with each stratified by two levels of fitness: good (no co-morbidity, not frail) and poor (co-morbidity score 2 or more, severe frailty).
Analysis for this study was conducted as a complete case analysis using Stata® 15.1 (StataCorp, College Station, TX, USA). All statistical tests were two-sided.
Results
The study analysed data on 83 188 women aged at least 50 years, who were newly diagnosed with unilateral early invasive breast cancer in NHS organizations in England and Wales between January 2014 and December 2017. Overall, 86.8 per cent of women had ER-positive and 13.2 per cent had ER-negative early invasive breast cancer, with similar percentages in each age group (Fig. 1).
Fig. 1.
Total number of women diagnosed with unilateral early invasive breast cancer and proportion with oestrogen receptor-negative disease in 2014–2017, by age group at diagnosis
EIBC, early invasive breast cancer; ER. oestrogen receptor.
Baseline patient and tumour characteristics for women with each ER status subtype are summarized by age group at diagnosis in Table 1. There were several differences in tumour characteristics across all age groups between women with ER-positive and those with ER-negative early invasive breast cancer. For example, women with ER-positive breast cancer were more likely to present with grade 2 tumours, whereas a greater proportion of women with ER-negative early invasive breast cancer had grade 3 tumours. The proportions of women with a HER2-negative subtype or nodal metastases (N1 category or above) were lower among those with ER-positive tumours. In contrast, there were few differences in patient demographics between women with ER-positive and ER-negative tumours. The prevalence of co-morbidity or frailty was, as expected, greater among older women, regardless of ER status.
Table 1 .
Baseline tumour and patient characteristics for women with oestrogen receptor-positive and oestrogen receptor-negative early invasive breast cancer by age group at diagnosis
| ER-positive EIBC |
ER-negative EIBC |
|||||
|---|---|---|---|---|---|---|
| 50–69 years (n=47 443) | 70–79 years (n=15 850) | ≥80 years (n=8878) | 50–69 years (n=7083) | 70–79 years (n=2498) | ≥80 years (n=1436) | |
| Invasive grade | ||||||
| G1 | 10 309 (21.7) | 2698 (17.0%) | 1394 (15.7) | 106 (1.5) | 42 (1.7) | 22 (1.5) |
| G2 | 27 771 (58.5) | 9909 (62.5) | 5803 (65.4) | 1558 (22.0) | 597 (23.9) | 342 (23.8) |
| G3 | 9363 (19.9) | 3243 (20.5) | 1681 (18.9) | 5419 (76.5) | 1858 (74.4) | 1072 (74.7) |
| Tumour size (mm) (T status) | ||||||
| 1–20 (T1) | 31 349 (66.1) | 8865 (55.9) | 3649 (41.1) | 3436 (48.5) | 1031 (41.3) | 407 (28.3) |
| 21–50 (T2) | 14 288 (30.1) | 6357 (40.1) | 4767 (53.7) | 3237 (45.7) | 1332 (53.3) | 889 (61.9) |
| ≥51(T3) | 1806 (3.8) | 628 (4.0) | 462 (5.2) | 410 (5.8) | 135 (5.4) | 140 (9.7) |
| Nodal status | ||||||
| N0 | 34 883 (73.5) | 11 665 (73.6) | 6795 (76.5) | 4915 (69.4) | 1712 (68.5) | 952 (66.3) |
| N1 | 10 899 (23.0) | 3520 (22.2) | 1776 (20.0) | 1884 (26.6) | 614 (24.6) | 352 (24.5) |
| ≥N2 | 1649 (3.5) | 658 (4.2) | 303 (3.4) | 282 (4.0) | 170 (6.8) | 131 (9.1) |
| HER2 status | ||||||
| Positive | 4681 (9.9) | 1305 (8.2) | 717 (8.1) | 1909 (27.0) | 589 (23.6) | 317 (22.1) |
| Negative | 39 544 (83.4) | 13 441 (84.8) | 7391 (83.3) | 4865 (68.7) | 1786 (71.5) | 1021 (71.1) |
| Borderline | 3218 (6.8) | 1104 (7.0) | 770 (8.7) | 309 (4.4) | 123 (4.9) | 98 (6.8) |
| Screen-detected method of presentation | ||||||
| No | 17 992 (37.9) | 10 522 (66.4) | 8448 (95.2) | 4344 (61.3) | 2026 (81.1) | 1393 (97.0) |
| Yes | 29 451 (62.1) | 5328 (33.6) | 430 (4.8) | 2739 (38.7) | 472 (18.9) | 43 (3.0) |
| Charlson Co-morbidity Index | ||||||
| 0 | 43 381 (91.4) | 12 999 (82.0) | 5903 (66.5) | 6445 (91.0) | 2004 (80.2) | 992 (69.1) |
| 1 | 3105 (6.5) | 1881 (11.9) | 1590 (17.9) | 453 (6.4) | 316 (12.7) | 242 (16.9) |
| ≥2 | 957 (2.0) | 970 (6.1) | 1385 (15.6) | 185 (2.6) | 178 (7.1) | 202 (14.1) |
| SCARF index | ||||||
| Fit | 39 385 (83.0) | 10 601 (66.9) | 4148 (46.7) | 5813 (82.1) | 1652 (66.1) | 715 (49.8) |
| Mild–moderate frailty | 5993 (12.6) | 3095 (19.5) | 1766 (19.9) | 929 (13.1) | 461 (18.5) | 261 (18.2) |
| Severe frailty | 2065 (4.4) | 2154 (13.6) | 2964 (33.4) | 341 (4.8) | 385 (15.4) | 460 (32.0) |
| Index of multiple deprivation | ||||||
| 1(most deprived) | 7264 (15.3) | 2170 (13.7) | 1300 (14.6) | 1251 (17.7) | 389 (15.6) | 223 (15.5) |
| 2 | 8567 (18.1) | 2724 (17.2) | 1631 (18.4) | 1362 (19.2) | 440 (17.6) | 280 (19.5) |
| 3 | 9821 (20.7) | 3298 (20.8) | 1914 (21.6) | 1427 (20.1) | 548 (21.9) | 296 (20.6) |
| 4 | 10 988 (23.2) | 3829 (24.2) | 2046 (23.0) | 1543 (21.8) | 535 (21.4) | 318 (22.1) |
| 5 (least deprived) | 10 803 (22.8) | 3829 (24.2) | 1987 (22.4) | 1500 (21.2) | 586 (23.5) | 319 (22.2) |
Values in parentheses are percentages. ER, oestrogen receptor; EIBC, early invasive breast cancer; HER2, human epidermal growth factor 2; SCARF, secondary care administrative records frailty.
Overall, 76 312 (91.7 per cent) of women had surgery, and the rate of surgery was observed to be lower in older women in both ER subgroups (Fig. 2). In women aged 70–74, 75–79 and 80 years or above, the proportions that did not have surgery in the ER-positive subgroup were 5.6, 11.0 and 41.9 per cent respectively. Corresponding values in the ER-negative subgroup were 3.8, 3.7 and 12.3 per cent. Among women who had surgery, the rate of mastectomy in contrast to BCS increased with age, irrespective of ER status. Table 2 gives the unadjusted percentages of women not receiving surgery in relation to individual patient and tumour factors.
Fig. 2.
Observed rate of mastectomy and breast-conserving surgery in women with unilateral early invasive breast cancer, by age at diagnosis and oestrogen receptor status
BCS, breast-conserving surgery; ER, oestrogen receptor; EIBC, early invasive breast cancer.
Table 2 .
Comparison of the influence of patient and tumour characteristics on the likelihood of not receiving surgery in women with oestrogen receptor-positive and oestrogen receptor-negative early invasive breast cancer
|
% not receiving surgery
|
Regression coefficient | P | ||
|---|---|---|---|---|
| ER-positive (n=72 171) | ER-negative (n=11 017) | |||
| Age at diagnosis (years) | ||||
| 50–59 | 2.7 | 3.6 | ||
| 60–69 | 3.1 | 3.2 | ||
| 70–79 | 7.9 | 3.8 | ||
| ≥80 | 41.9 | 12.3 | ||
| Age spline 1 | 0 | <0.001 | ||
| Age spline 2 | −0.01 (−0.03, 0.00) | |||
| Age spline 3 | 0.10 (0.08, 0.12) | |||
| Age spline 4 | 0.05 (−0.08, 0.18) | |||
| Age spline 1 × ER-negative | 0 | <0.001 | ||
| Age spline 2 × ER-negative | 0.01 (−0.02, 0.03) | |||
| Age spline 3 × ER-negative | −0.08 (−0.12, −0.04) | |||
| Age spline 4 × ER-negative | 0.34 (0.04, 0.64) | |||
| Invasive grade | ||||
| G1 | 7.8 | 5.3 | 0 | <0.001 |
| G2 | 9.6 | 6.1 | −0.07 (−0.17, 0.03) | |
| G3 | 7.3 | 4.2 | −0.41 (−0.54, −0.28) | |
| Tumour size (mm) (T category) | ||||
| 1–20 (T1) | 6.3 | 3.2 | 0 | <0.001 |
| 21–50 (T2) | 12.9 | 5.2 | 0.34 (0.25, 0.42) | |
| ≥51 (T3) | 11.6 | 8.2 | 0.51 (0.33, 0.68) | |
| Node category | ||||
| N0 | 9.6 | 4.2 | 0 | <0.001 |
| N1 | 7.0 | 6.1 | −0.41 (−0.52, −0.29) | |
| N2 | 3.3 | 2.7 | −1.37 (−1.67, −1.07) | |
| N0 × ER-negative | 0 | <0.001 | ||
| N1 × ER-negative | 0.72 (0.51, 0.92) | |||
| N2 × ER-negative | 0.60 (−0.08, 1.28) | |||
| ER status | ||||
| Positive | 8.8 | – | 0 | 0.750 |
| Negative | – | 4.6 | −0.23 (−1.67, 1.20) | |
| HER2 status | ||||
| Positive | 7.9 | 5.0 | 0 | <0.001 |
| Negative | 8.7 | 4.4 | −0.10 (−0.22, 0.01) | |
| Borderline | 12.0 | 6.0 | 0.16 (−0.01, 0.33) | |
| Screen-detected cancer | ||||
| No | 15.1 | 5.7 | 0 | <0.001 |
| Yes | 2.2 | 2.1 | −0.86 (−0.86, −0.66) | |
| Charlson Co-morbidity Index | ||||
| 0 | 5.8 | 3.9 | 0 | <0.001 |
| 1 | 19.5 | 6.6 | 0.35 (0.23, 0.48) | |
| ≥2 | 44.1 | 12.9 | 1.03 (0.90, 1.16) | |
| SCARF index | ||||
| Fit | 4.8 | 3.7 | 0 | <0.001 |
| Mild–moderate frailty | 10.1 | 5.1 | 0.24 (0.14, 0.34) | |
| Severe frailty | 36.9 | 10.5 | 0.94 (0.81, 1.06) | |
| Fit × ER-negative | 0 | <0.001 | ||
| Mild–moderate frailty × ER-negative | −0.16 (−0.38, 0.06) | |||
| Severe frailty × ER-negative | −0.97 (−1.17, −0.77) | |||
Values in parentheses are 95 per cent confidence intervals. ER, oestrogen receptor; HER2, human epidermal growth factor receptor 2; SCARF, secondary care administrative records frailty.
The multivariable regression model used to examine the likelihood of no surgery contained all of the patient and tumour factors except deprivation quintile. This model had good calibration and discrimination (overall c-statistic 0.84). The model coefficients for each of the explanatory variables are shown in Table 2. In addition to age, the model revealed that lower grade, absence of malignant lymph nodes and poor patient fitness were strongly associated with an increased likelihood of not receiving surgery for early invasive breast cancer.
Fig. 3 shows the predicted likelihood of not having surgery by age at diagnosis for the four patient subgroups. In each subgroup, the estimated rates for women with ER-positive and ER-negative early invasive breast cancer diverge as age at diagnosis increases. Each subgroup shows a different degree of separation, with changes in rates of surgery occurring predominantly in women with ER-positive breast cancer. In women with a high burden of co-morbidity (CCI score 2 or more) or severe frailty, the proportion of women with ER-positive breast cancer not having surgery increases as age at diagnosis extends above 70 years. Less than 50 per cent of women aged 85 years or above had surgery in both the low-risk (Fig. 3c) and high-risk (Fig. 3d) subgroups. In women with no co-morbidity or frailty, the increase in the proportion of women with ER-positive disease not having surgery was less marked, particularly among women with high-risk disease.
Fig. 3.
Predicted rate of surgery for women with oestrogen receptor-positive and oestrogen receptor-negative early invasive breast cancer, by age at diagnosis for four risk subgroups
a Low-risk early invasive breast cancer (EIBC) (grade 1, stage T1 N0), no co-morbidity or frailty; b high-risk EIBC (grade 3, stage T2 N1), no co-morbidity or frailty; c low-risk EIBC, severe co-morbidity or frailty; d high-risk EIBC, severe co-morbidity or frailty. ER, oestrogen receptor.
In contrast, among women with ER-negative disease, the relationship between age and the likelihood of not receiving surgery was largely unchanged by the level of either tumour risk or physical fitness. Lastly, except for women with low-risk early invasive breast cancer and poor physical fitness, estimated rates of surgery among women aged 50–65 years were similar (Fig. S1).
Table 3 shows the percentage of women with a postoperative inpatient stay exceeding 48 h and other selected short-term outcomes. Differences between ER-positive and ER-negative groups, although statistically significant, were small. The risk of 30-day postoperative mortality was less than 1 in 500 women for both ER-positive and ER-negative groups, and rates of 30-day emergency readmission were also low (less than 3 per cent). Across all ER subgroups, more women aged 70 years or above had a longer hospital stay after breast surgery than women aged 50–69 years. The difference in the proportion of women with a prolonged hospital stay was greater between the age groups than between women with ER-positive and ER-negative early invasive breast cancer.
Table 3 .
Length of stay and short-term outcomes after breast surgery in women diagnosed with early invasive breast cancer in the NHS in England and Wales in 2014–2017, by age and oestrogen receptor status
| Age 50–69 years |
Age ≥70 years |
|||
|---|---|---|---|---|
| ER-positive | ER-negative | ER-positive | ER-negative | |
| No. of women having surgery | ||||
| BCS | 35 222 | 4778 | 12 919 | 1842 |
| With SN biopsy | 29 941 | 3572 | 6681 | 1414 |
| Mastectomy | 10 837 | 2064 | 6828 | 1822 |
| With SN biopsy | 6681 | 1119 | 4361 | 994 |
| Length of stay after surgery ≥2 days | ||||
| BCS with SN biopsy | 1393 (4.7) | 181 (5.1) | 779 (11.7) | 127 (9.0) |
| Simple mastectomy with SN biopsy | 1131 (16.9) | 204 (18.2) | 1515 (34.7) | 385 (38.7) |
| Short-term outcomes after any breast surgery | ||||
| 30-day postoperative mortality | 6 (0.01) | 4 (0.06) | 9 (0.05) | 7 (0.19) |
| Emergency inpatient re-admission within 30 days of discharge | 385 (0.8) | 147 (2.1) | 226 (1.1) | 92 (2.5) |
Values in parentheses are percentages. ER, oestrogen receptor; BCS, breast-conserving surgery; SN, sentinel node.
Discussion
In this study of women aged 50 years or above diagnosed with unilateral early invasive breast cancer in England and Wales, 86.8 per cent of women had ER-positive and 13.2 per cent had ER-negative breast cancer. These proportions were unaffected by age at diagnosis. In the analysis of treatment patterns for this cohort, older age at diagnosis was associated with a reduced likelihood of having surgery, and this relationship differed according to ER status. Overall, only 8.3 per cent of women did not have surgery, but in women aged 80 years or more the proportions for ER-positive and ER-negative subgroups were 41.9 per cent and 12.3 per cent respectively. For women with ER-positive early invasive breast cancer, the relationship between likelihood of surgery and age was influenced strongly by the level of tumour risk and physical fitness. In contrast, among women with ER-negative breast cancer, the influence of these factors was less marked. Although the co-morbidity burden level and frailty among older women was similar across the ER-status subgroups, the short-term outcomes after breast surgery were broadly similar despite a higher proportion of women with ER-negative early invasive breast cancer receiving surgery.
Currently, few studies of treatment patterns provide results for both ER-positive and ER-negative subgroups of older women with breast cancer. When considered as separate cohorts, the observed rate of surgery among women aged 70 years or above with ER-positive early invasive breast cancer in this study was higher than rates of 54–72 per cent reported in earlier UK-based studies3,4,11. Yet, this rate of surgery for women with ER-positive breast cancer remains lower than rates reported in countries such as the Netherlands and the USA23–25. In comparison, a population-level study26 of treatment patterns in older women with ER-negative breast cancer in the USA reported rates of surgery that were similar to those reported in the present study.
There is no evidence to support a different approach to primary treatment for early invasive breast cancer in older women based solely on ER status. Primary endocrine treatment is available as a systemic treatment option for older women with ER-positive breast cancer and poor fitness, but there is no equivalent alternative for women with ER-negative breast cancer. It would not be appropriate for all older women with early invasive breast cancer to be offered surgery regardless of their functional or fitness level27. It may, however, be that health professionals are more inclined to offer surgery to older women with ER-negative breast cancer and co-morbidity or frailty than their ER-positive counterparts. A noteworthy result from this study is the greater proportion of older women with ER-positive breast cancer not undergoing surgery despite no record of co-morbidity or frailty. This is inconsistent with International Society of Geriatric Oncology/ European Society of Breast Cancer Specialists recommendations that ‘Primary endocrine treatment should only be offered to elderly individuals with ER-positive tumours who have a short estimated life-expectancy (<2–3 years), who are considered unfit for surgery after optimization of medical conditions…’9. Although patient preferences may account for some of the differences in the rate of surgery between women with ER-positive and ER-negative breast cancer, these are likely to be influenced strongly by the advice given by their health professionals28,29.
The estimation of life expectancy among older patients with breast cancer is complex, and has been shown to be inconsistent among healthcare professionals30. For patients whose life expectancy is underestimated, it is possible that the current recommendations for older women with ER-positive early breast cancer2,9 are leading to less advocacy for surgical resection when treatment options are discussed. This is despite little evidence to suggest that older age is associated with a higher risk of adverse surgical outcomes after breast surgery31. Inconsistencies in assessing the prognosis from early invasive breast cancer and competing risks of death from underlying co-morbidity and frailty are also likely to contribute to this. In addition, few UK breast cancer units have designated specialists or operational dedicated service pathways objectively to assess and optimize patient fitness for surgery30.
There are several strengths to this study. The study used information from national cancer registration data that was linked to routinely collected administrative data sets, using pseudonymized patient identifiers. This approach produced a patient cohort that is likely to be an accurate representation of current clinical practice in England and Wales. Moreover, the regression model developed during the analysis demonstrated good calibration and discrimination, suggesting that the predictions describing the influence of age on the rate of surgery for ER-positive and ER-negative early invasive breast cancer are reliable.
The study also has several limitations. Routinely collected cancer registration and hospital data may contain errors in the coding of surgical procedures, which could influence the estimated treatment rates. Validation work, however, has shown HES to capture major procedures accurately, with 90–93 per cent agreement with data provided by surgeons32. These data sets, moreover, have few data items on measures of patient fitness7. This study therefore adopted a similar methodology to that of other UK-based studies3,11 and used the diagnostic information in the administrative data sets to derive measures of fitness (CCI and SCARF index). Given that administrative data sets such as HES and PEDW do not capture all co-morbid conditions, this approach may underestimate the burden of poor fitness within this cohort. Nonetheless, the study observed the expected increase in prevalence of co-morbidity and frailty with older age. Lastly, the results were based on a complete case analysis, with 10.0 per cent of records dropped because they did not have a known ER status and a further 13.7 per cent dropped because of missing values (mostly related to HER2 status; 7.7 per cent). This might introduce bias in the observed relationship between ER status and outcomes, but the effect is likely to be small. Furthermore, the distributions of missing data were similar among women with ER-positive and ER-negative, so it is unlikely that any issues in data capture would affect the two ER status subgroups differently.
The proportion of women receiving surgery for ER-positive early invasive breast cancer in England and Wales decreased at a faster rate with older age, compared with that in women with ER-negative breast cancer. Moreover, the relationship between the likelihood of surgery and age was influenced strongly by the level of tumour risk and degree of patient fitness among women with ER-positive early invasive breast cancer. The reasons for these observed differences in treatment patterns, especially in the absence of poor fitness, are unclear. Assessment for suitability and advice for surgery should be consistent for all older women with early invasive breast cancer, and clinical guidelines should aim to be clear and objective in their recommendations.
Supplementary Material
Acknowledgements
This work used data provided by patients and collected by the NHS as part of their care and support. The data are collated, maintained and quality assured by the National Cancer Registration and Analysis Service, which is part of Public Health England. Access to the data was facilitated by the PHE Office for Data Release. No additional data are available. Data on English cancer registrations can be accessed via the Office for Data Release at Public Health England (https://www.gov.uk/government/publications/accessing-public-health-england-data/about-the-phe-odr-and-accessing-data).
This study was undertaken as part of the work by the NABCOP. The Audit is commissioned by the Healthcare Quality Improvement Partnership (HQIP) as part of the National Clinical Audit and Patient Outcomes Programme, and funded by NHS England and the Welsh Government (www.hqip.org.uk/national-programmes). Neither HQIP nor the funders had any involvement in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. The authors had full independence from the HQIP. The aim of the NABCOP is to evaluate the care of older women with breast cancer in England and Wales, and support NHS providers to improve the quality of hospital care for these women. More information can be found at www.nabcop.org.uk.
D.D. also receives funding from Cancer Research UK (grant C8225/A21133).
Disclosure. The authors declare no conflict of interest.
Supplementary material
Supplementary material is available at BJS online.
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