Summary Background Investigators of registry-based studies report improved survival for breast-conserving surgery plus radiotherapy compared with mastectomy in early breast cancer. As these studies ...did not present long-term overall and breast cancer-specific survival, the effect of breast-conserving surgery plus radiotherapy might be overestimated. In this study, we aimed to evaluate 10 year overall and breast cancer-specific survival after breast-conserving surgery plus radiotherapy compared with mastectomy in Dutch women with early breast cancer. Methods In this population-based study, we selected all women from the Netherlands Cancer Registry diagnosed with primary, invasive, stage T1–2, N0–1, M0 breast cancer between Jan 1, 2000, and Dec 31, 2004, given either breast-conserving surgery plus radiotherapy or mastectomy, irrespective of axillary staging or dissection or use of adjuvant systemic therapy. Primary outcomes were 10 year overall survival in the entire cohort and breast cancer-specific survival in a representative subcohort of patients diagnosed in 2003 with characteristics similar to the entire cohort. We estimated breast cancer-specific survival by calculating distant metastasis-free and relative survival for every tumour and nodal category. We did multivariable Cox proportional hazard analysis to estimate hazard ratios (HRs) for overall and distant metastasis-free survival. We estimated relative survival by calculating excess mortality ratios using life tables of the general population. We did multiple imputation to account for missing data. Findings Of the 37 207 patients included in this study, 21 734 (58%) received breast-conserving surgery plus radiotherapy and 15 473 (42%) received mastectomy. The 2003 representative subcohort consisted of 7552 (20%) patients, of whom 4647 (62%) received breast-conserving surgery plus radiotherapy and 2905 (38%) received mastectomy. For both unadjusted and adjusted analysis accounting for various confounding factors, breast-conserving surgery plus radiotherapy was significantly associated with improved 10 year overall survival in the whole cohort overall compared with mastectomy (HR 0·51 95% CI 0·49–0·53; p<0·0001; adjusted HR 0·81 0·78–0·85; p<0·0001), and this improvement remained significant for all subgroups of different T and N stages of breast cancer. After adjustment for confounding variables, breast-conserving surgery plus radiotherapy did not significantly improve 10 year distant metastasis-free survival in the 2003 cohort overall compared with mastectomy (adjusted HR 0·88 0·77–1·01; p=0·07), but did in the T1N0 subgroup (adjusted 0·74 0·58–0·94; p=0·014). Breast-conserving surgery plus radiotherapy did significantly improve 10 year relative survival in the 2003 cohort overall (adjusted 0·76 0·64–0·91; p=0·003) and in the T1N0 subgroup (adjusted 0·60 0·42–0·85; p=0·004) compared with mastectomy. Interpretation Adjusting for confounding variables, breast-conserving surgery plus radiotherapy showed improved 10 year overall and relative survival compared with mastectomy in early breast cancer, but 10 year distant metastasis-free survival was improved with breast-conserving surgery plus radiotherapy compared with mastectomy in the T1N0 subgroup only, indicating a possible role of confounding by severity. These results suggest that breast-conserving surgery plus radiotherapy is at least equivalent to mastectomy with respect to overall survival and may influence treatment decision making for patients with early breast cancer. Funding None.
Here we report for the first time the relation between breast cancer subtypes and 10‐year recurrence rates and mortality in the Netherlands. All operated women diagnosed with invasive non‐metastatic ...breast cancer in 2005 in the Netherlands were included. Patients were classified into breast cancer subtypes according to ER, PR, HER2 status and grade: luminal A, luminal B, HER2 positive and triple negative. Percentages and hazards of recurrence were compared among subtypes. Adjusted 10‐year overall (OS) and recurrence‐free survival (RFS) were calculated using multivariable Cox regression. Of 8,062 patients, 4,482 (56%) were luminal A, 2,090 (26%) luminal B, 504 (6%) HER2 positive and 986 (12%) triple negative. Local recurrences (7.5%) and distant metastases (25.6%) occurred most often in HER2 positive disease and the least often in luminal A (3.7% and 9.5%, respectively). Regional recurrences were most often diagnosed in triple negative disease (5.2%), and the least often in luminal A (1.7%). HER2 positive and triple negative subtypes had the highest recurrence rates in the second year, while luminal A and B showed a more continuous pattern over time, with lobular tumours recurring more often. After adjustment for differences in baseline characteristics, triple negative disease showed worse 10‐year OS and triple negative and HER2 positive disease had the lowest 10‐year RFS. In the Netherlands, breast cancer subtypes are important predictors for 10‐year recurrence rates. Knowledge on recurrence and survival rates according to these different subtypes, in combination with other prognostic factors, can support patient‐tailored treatment and individualised follow‐up.
What's new?
While breast cancer subtypes are known independent predictors of survival and recurrence risk, data on long‐term recurrences in daily practice remain scarce. In this population‐based study reporting on 10‐year recurrences, HER2 positive and triple negative subtypes showed the highest recurrence rates, which occurred most often in the second year, while luminal A and B recurred later on during the follow‐up. Lobular tumours recurred more often than ductal tumours. In the Netherlands, breast cancer subtypes are thus important predictors for 10‐year recurrence rates. Knowledge on recurrence and survival rates according to these different subtypes can help support patient‐tailored treatment and individualised follow‐up.
This large population‐based study compared breast‐conserving surgery with radiation therapy (BCT) with mastectomy on (long‐term) breast cancer‐specific (BCSS) and overall survival (OS), and ...investigated the influence of several prognostic factors. Patients with primary T1‐2N0‐2M0 breast cancer, diagnosed between 1999 and 2012, were selected from the Netherlands Cancer Registry. We investigated the 1999–2005 (long‐term outcome) and the 2006–2012 cohort (contemporary adjuvant systemic therapy). Cause of death was derived from the Statistics Netherlands (CBS). Multivariable analyses, per time cohort, were performed in T1‐2N0‐2, and separately in T1‐2N0‐1 and T1‐2N2 stages. The T1‐2N0‐1 stages were further stratified for age, hormonal receptor and HER2 status, adjuvant systemic therapy and comorbidity. In total, 129,692 patients were included. In the 1999–2005 cohort, better BCSS and OS for BCT than mastectomy was seen in all subgroups, except in patients < 40 years with T1‐2N0‐1 stage. In the 2006–2012 cohort, superior BCSS and OS were found for T1‐2N0‐1, but not for T1‐2N2. Subgroup analyses for T1‐2N0‐1 showed superior BCSS and OS for BCT in patients >50 years, not treated with chemotherapy and with comorbidity. Both treatments led to similar BCSS in patients <50 years, without comorbidity and those treated with chemotherapy. Although confounding by severity and residual confounding cannot be excluded, this study showed better long‐term BCSS for BCT than mastectomy. Even with more contemporary diagnostics and therapies we identified several subgroups that may benefit from BCT. Our results support the hypothesis that BCT might be preferred in most breast cancer patients when both treatments are suitable.
What's new?
While breast‐conserving therapy (BCT) and mastectomy have long been considered equivalent in terms of survival in early‐stage breast cancer, recent studies suggest BCT offers superior survival over mastectomy. The findings of this study support that idea, showing that breast cancer‐specific survival and overall survival were greater for BCT than mastectomy in analyses of 129,692 patients diagnosed with breast cancer in The Netherlands between 1999 and 2012. Subgroup analyses revealed better survival for BCT in most instances, with survival being similar for BCT and mastectomy primarily among patients under age 50, patients without comorbidity, and those treated with chemotherapy.
Purpose
To extend the functionality of the existing INFLUENCE nomogram for locoregional recurrence (LRR) of breast cancer toward the prediction of secondary primary tumors (SP) and distant metastases ...(DM) using updated follow-up data and the best suitable statistical approaches.
Methods
Data on women diagnosed with non-metastatic invasive breast cancer were derived from the Netherlands Cancer Registry (
n
= 13,494). To provide flexible time-dependent individual risk predictions for LRR, SP, and DM, three statistical approaches were assessed; a Cox proportional hazard approach (COX), a parametric spline approach (PAR), and a random survival forest (RSF). These approaches were evaluated on their discrimination using the Area Under the Curve (AUC) statistic and on calibration using the Integrated Calibration Index (ICI). To correct for optimism, the performance measures were assessed by drawing 200 bootstrap samples.
Results
Age, tumor grade, pT, pN, multifocality, type of surgery, hormonal receptor status, HER2-status, and adjuvant therapy were included as predictors. While all three approaches showed adequate calibration, the RSF approach offers the best optimism-corrected 5-year AUC for LRR (0.75, 95%CI: 0.74–0.76) and SP (0.67, 95%CI: 0.65–0.68). For the prediction of DM, all three approaches showed equivalent discrimination (5-year AUC: 0.77–0.78), while COX seems to have an advantage concerning calibration (ICI < 0.01). Finally, an online calculator of INFLUENCE 2.0 was created.
Conclusions
INFLUENCE 2.0 is a flexible model to predict time-dependent individual risks of LRR, SP and DM at a 5-year scale; it can support clinical decision-making regarding personalized follow-up strategies for curatively treated non-metastatic breast cancer patients.
Purpose
To analyze the influence of hormone receptors (HR) and Human Epidermal growth factor Receptor-2 (HER2)-based molecular subtypes in stage III inflammatory breast cancer (IBC) on tumor ...characteristics, treatment, pathologic response to neoadjuvant chemotherapy (NACT), and overall survival (OS).
Methods
Patients with stage III IBC, diagnosed in the Netherlands between 2006 and 2015, were classified into four breast cancer subtypes: HR+/HER2− , HR+/HER2+ , HR−/HER2+ , and HR−/HER2− . Patient-, tumor- and treatment-related characteristics were compared. In case of NACT, pathologic complete response (pCR) was compared between subgroups. OS of the subtypes was compared using Kaplan–Meier curves and the log-rank test.
Results
1061 patients with stage III IBC were grouped into subtypes: HR+/HER2− (
N
= 453, 42.7%), HR−/HER2− (
N
= 258, 24.3%), HR−/HER2+ (
N
= 180,17.0%), and HR+/HER2+ (
N
= 170,16.0%). In total, 679 patients (85.0%) received NACT. In HR−/HER2+ tumors, pCR rate was highest (43%, (
p
< 0.001). In case of pCR, an improved survival was observed for all subtypes, especially for HR+/HER2+ and HR−/HER2+ tumor subtypes. Trimodality therapy (NACT, surgery, radiotherapy) improved 5-year OS as opposed to patients not receiving this regimen: HR+/HER2− (74.9 vs. 46.1%), HR+/HER2+ (80.4 vs. 52.6%), HR−/HER2+ (76.4 vs. 29.7%), HR−/HER2− (47.6 vs. 27.8%).
Conclusions
In stage III IBC, breast cancer subtypes based on the HR and HER2 receptor are important prognostic factors of response to NACT and OS. Patients with HR−/HER2− IBC were less likely to achieve pCR and had the worst OS, irrespective of receiving most optimal treatment regimen to date (trimodality therapy).
Survival estimates from diagnosis are of limited importance for (ex-)breast cancer patients who survived several years, as it includes information on already deceased patients. This study analysed ...the 10-year conditional risk of recurrent breast cancer in specific prognostic subgroups. Second, we investigated 10-year conditional overall survival (OS) and relative survival (RS), adjusted for confounding.
All women diagnosed in 2005 with operated T1-2N0-1 breast cancer were selected from the Netherlands Cancer Registry. Patients were classified into T1N0, T1N1, T2N0 and T2N1 stage. Ten-year conditional recurrence rates were calculated from diagnosis, and for patients without an event (local LR, regional recurrence RR, distant metastasis DM or death) every year following diagnosis. Ten-year conditional OS was calculated using multivariable Cox regression. RS was estimated by dividing patient survival rates by those of the general Dutch population.
We included 7969 patients: 52.3% had T1N0, 15.3% T1N1, 19.9% T2N0 and 12.5% T2N1 stage. For T1N0, 10-year LR rates changed from 4.6% at diagnosis to 0.5% in year 10. RR rates changed from 2.3% to 0.2%, and DM rates changed from 7.8% to 0.6%. For T2N1 stage, the LR, RR and DM rates changed from 6.2% to 0.8%, 5.2%–0.4% and 19.6%–1.5%, respectively. For the luminal A subtype, LR, RR and DM rates changed from 3.9% to 0.4%, 1.7%–0.5% and 7.3%–1.1%, while for triple negative, these rates changed from 5.6% to 0.7%, 4.9%–0.2% and 16.7%–0%, respectively. Differences between subgroups attenuated over time, and all recurrence rates became ≤1.5% in year 10. Ten-year OS and RS, adjusted for confounding, showed declining risk differences between subgroups over time.
Differences in recurrence rates, OS and RS between prognostic subgroups declined as years passed by. These results highlight the importance of taking into account disease-free years to more accurately predict (ex-)breast cancer patients' prognosis over time.
•Survival estimates from diagnosis are less important for breast cancer survivors.•Conditional survival includes the numbers of years survived following diagnosis.•Differences in recurrence risks between prognostic subgroups declined over time.•Differences in overall and relative survival between subgroups declined as well.•Conditional survival and recurrences provide patients better insight in prognosis.
Purpose
In this study, we explored how patients experience current information provision and decision-making about post-treatment surveillance after breast cancer. Furthermore, we assessed patients’ ...perspectives regarding less intensive surveillance in case of a low risk of recurrence.
Methods
We conducted semi-structured interviews with 22 women in the post-treatment surveillance trajectory in seven Dutch teaching hospitals.
Results
Although the majority of participants indicated a desire for shared decision-making (SDM) about post-treatment surveillance, participants experienced no SDM. Information provision was often suboptimal and unstructured. Participants were open for using risk information in decision-making, but hesitant towards less intensive surveillance. Perceived advantages of less intensive surveillance were: less distressing moments, leaving the patient role behind, and lower burden. Disadvantages were: fewer moments for reassurance, fear of missing recurrences, and a higher threshold for aftercare for side effects.
Conclusions
SDM about post-treatment surveillance is desirable. Although women are hesitant about less intensive surveillance, they are open to the use of personalised risk assessment for recurrences in decision-making about surveillance.
Implications for Cancer Survivors
To facilitate SDM about post-treatment surveillance, the timing and content of information provision should be improved. Risk information should be provided in an accessible and understandable way. Moreover, fear of cancer recurrence and other personal considerations should be addressed in the process of SDM.
No studies are available in which changes over time in characteristics and prognosis of patients with interval breast cancers (ICs) and screen-detected breast cancers (SDCs) have been compared. The ...aim was to study these trends between 1995 and 2018.
All women with invasive SDCs (N = 4290) and ICs (N = 1352), diagnosed in a southern mammography screening region in the Netherlands, were included and followed until date of death or 31 December 2022.
The 5-year overall survival rate of women with SDCs increased from 91.4% for those diagnosed in 1995-1999 to 95.0% for those diagnosed in 2013-2018 (P < 0.001), and from 74.8 to 91.6% (P < 0.001) in the same periods for those with ICs. A similar trend was observed for the 10-year survival rates. After adjustment for changes in tumour characteristics, the hazard ratio (HR) for overall survival was 0.47 (95% confidence interval (CI): 0.38-0.59) for women with SDCs diagnosed in the period 2013-2018, compared to the women diagnosed in the period 1995-1999. For the women with ICs this HR was 0.27 (95% CI: 0.19-0.40).
The prognosis of women with ICs has improved rapidly since 1995 and is now almost similar to that of women with SDCs.
Background
This study aimed to examine the association between preoperative magnetic resonance imaging (MRI) and surgical margin involvement, as well as to determine the factors associated with ...positive resection margins in screen-detected breast cancer patients undergoing breast-conserving surgery (BCS).
Methods
Breast cancer patients eligible for BCS and diagnosed after biennial screening mammography in the south of The Netherlands (2008–2017) were retrospectively included. Missing values were imputed and multivariable regression analyses were performed to analyze whether preoperative MRI was related to margin involvement after BCS, as well as to examine what factors were associated with positive resection margins, defined as more than focally (>4 mm) involved.
Results
Overall, 2483 patients with invasive breast cancer were enrolled, of whom 123 (5.0%) had more than focally involved resection margins. In multivariable regression analyses, preoperative MRI was associated with a reduced risk of positive resection margins after BCS (adjusted odds ratio OR 0.56, 95% confidence interval CI 0.33–0.96). Lobular histology (adjusted OR 2.86, 95% CI 1.68–4.87), large tumor size (per millimeter increase, adjusted OR 1.05, 95% CI 1.03–1.07), high (>75%) mammographic density (adjusted OR 3.61, 95% CI 1.07–12.12), and the presence of microcalcifications (adjusted OR 4.45, 95% CI 2.69–7.37) and architectural distortions (adjusted OR 1.85, 95% CI 1.01–3.40) were independently associated with positive resection margins after BCS.
Conclusions
Preoperative MRI was associated with lower risk of positive resection margins in patients with invasive breast cancer eligible for BCS using multivariable analysis. Furthermore, specific mammographic characteristics and tumor characteristics were independently associated with positive resection margins after BCS.
Background
Seroma is a frequent problem after mastectomy (ME) and axillary lymph node dissection (ALND). Seroma is associated with pain, discomfort, impaired mobilisation and repeated aspirations, ...often resulting in a surgical site infection (SSI). It has already been demonstrated that minimizing dead space through fixation of the skin flaps to the underlying muscles (quilting) lowers the incidence of seroma. The aim of this study was to evaluate the effect of quilting on the incidence of seroma, and SSI.
Methods
Two consecutive groups with a total of 176 patients following ME and/or ALND were retrospectively compared. Endpoints were the incidence of seroma, and number and volume of aspirations and SSIs. Analysed risk factors were age, ME, lymph node dissection, neoadjuvant therapy, body mass index (BMI) and hypertension.
Results
The quilted group (
n
= 89) scored significantly better on all endpoints compared with the conventional group (
n
= 87). The incidence of seroma decreased from 80.5 % to 22.5 % (
p
< 0.01), the mean number of aspirations from 4.86 to 2.40 (
p
= 0.015), the volume of aspirations from 1660 ml to 611 ml (
p
= 0.05) and the SSIs from 31.0 % to 11.2 % (
p
< 0.01). Increasing age and lymph node dissection were found to be risk factors for seroma; quilting was a protective factor.
Conclusion
Quilting is an effective method for preventing seroma and its complications.
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