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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. 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. 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. 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. None.

PurposeTo 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.MethodsData 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.ResultsAge, 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.ConclusionsINFLUENCE 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.

Primary chemotherapy in breast cancer poses a dilemma with regard to adjuvant locoregional radiotherapy, as guidelines for locoregional radiotherapy were originally based on pathology results of primary surgery. We aimed to evaluate the oncological safety of de-escalated locoregional radiotherapy in patients with cT1–2N1 breast cancer treated with primary chemotherapy, according to a predefined, consensus-based study guideline. In this prospective registry study (RAPCHEM, BOOG 2010–03), patients referred to one of 17 participating radiation oncology centres in the Netherlands between Jan 1, 2011, and Jan 1, 2015, with cT1–2N1 breast cancer (one to three suspicious nodes on imaging before primary chemotherapy, of which at least one had been pathologically confirmed), and who were treated with primary chemotherapy and surgery of the breast and axilla were included in the study. The study guideline comprised three risk groups for locoregional recurrence, with corresponding locoregional radiotherapy recommendations: no chest wall radiotherapy and no regional radiotherapy in the low-risk group, only local radiotherapy in the intermediate-risk group, and locoregional radiotherapy in the high-risk group. Radiotherapy consisted of a biologically equivalent dose of 25 fractions of 2 Gy, with or without a boost. During the study period, the generally applied radiotherapy technique in the Netherlands was forward-planned or inverse-planned intensity modulated radiotherapy. 5-year follow-up was assessed, taking into account adherence to the study guideline, with locoregional recurrence rate as primary endpoint. We hypothesised that 5-year locoregional recurrence rate would be less than 4% (upper-limit 95% CI 7·8%). This study was registered at ClinicalTrials.gov, NCT01279304, and is completed. 838 patients were eligible for 5-year follow-up analyses: 291 in the low-risk group, 370 in the intermediate-risk group, and 177 in the high-risk group. The 5-year locoregional recurrence rate in all patients was 2·2% (95% CI 1·4–3·4). The 5-year locoregional recurrence rate was 2·1% (0·9–4·3) in the low-risk group, 2·2% (1·0–4·1) in the intermediate-risk group, and 2·3% (0·8–5·5) in the high-risk group. If the study guideline was followed, the locoregional recurrence rate was 2·3% (0·8–5·3) for the low-risk group, 1·0% (0·2–3·4) for the intermediate-risk group, and 1·4% (0·3–4·5) for the high-risk group. In this study, the 5-year locoregional recurrence rate was less than 4%, which supports our hypothesis that it is oncologically safe to de-escalate locoregional radiotherapy based on locoregional recurrence risk, in selected patients with cT1–2N1 breast cancer treated with primary chemotherapy, according to this predefined, consensus-based study guideline. Dutch Cancer Society. For the Dutch translation of the abstract see Supplementary Materials section.

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.

BackgroundThis 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).MethodsBreast 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.ResultsOverall, 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.ConclusionsPreoperative 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.

PurposeTo 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).MethodsPatients 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.Results1061 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%).ConclusionsIn 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).

Background 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. Methods 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. Results 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). Conclusion The prognosis of women with ICs has improved rapidly since 1995 and is now almost similar to that of women with SDCs.

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.

Objectives We determined the failure rate of stereotactic core needle biopsy (SCNB) and its causes and final outcome in women recalled for calcifications at screening mammography. Methods We included a consecutive series of 624,039 screens obtained in a Dutch screening region between January 2009 and July 2019. Radiology reports and pathology results were obtained of all recalled women during 2-year follow-up. Results A total of 3495 women (19.6% of 17,809 recalls) were recalled for suspicious calcifications. SCNB was indicated in 2818 women, of whom 12 had incomplete follow-up and another 12 women refused biopsy. DCIS or invasive cancer was diagnosed in 880 of the remaining 2794 women (31.5%). SCNB failed in 62 women (2.2%, 36/2794). These failures were mainly due to a too posterior ( n = 30) or too superficial location ( n = 17) of the calcifications or calcifications too faint for biopsy ( n = 13). Of these 62 women, 10 underwent surgical biopsy, yielding one DCIS (intermediate grade) and two invasive cancers (one intermediate grade and one high grade) and another two women were diagnosed with DCIS (both high grade) at follow-up. Thus, the malignancy rate after SCNB failure was 8.1% (5/62). Calcifications were depicted neither at SCNB specimen radiography nor at pathology in 16 women after (repeated) SCNB (0.6%, 31/2732). None of them proved to have breast cancer at 2-year follow-up. Conclusions The failure rate of SCNB for suspicious calcifications is low but close surveillance is warranted, as breast cancer may be present in up to 8% of these women. Key Points • The failure rate of stereotactic core needle biopsy (SCNB) for calcifications recalled at screening mammography was 2.2%. • Failures were mainly due to calcifications that could not be reached by SCNB or calcifications too faint for biopsy. • The management after failed SCNB was various. At least, close surveillance with a low threshold for surgical biopsy is recommended as breast cancer may be present in up to 8% of women with SCNB failure.

Introduction Consensus about surgical treatment options for breast cancer in elderly patients remains elusive due to exclusion from clinical trials. Fear of complications due to increased age often is an important factor in the choice of treatment and might result in different treatment of the older patient. Methods A total of 1258 female patients who underwent breast cancer surgery for primary diagnosed breast cancer in 2010–2014 were included. Incidence of postoperative complications (POCs) was compared between the younger (18–70 years, N  = 1008) and older (≥71 years, N  = 250) patients. Multivariate logistic regression was performed to identify the correlation between age and POCs. Results POCs developed in 25.9% of the younger and 31.6% of the older patients ( p  = 0.042). In multivariable logistic regression analysis of the overall study population, age was no risk factor for POC (odds ratio 0.950, 95% confidence interval 0.640–1.410, p  = 0.798). More extensive surgery (mastectomy and/or axillary lymph node dissection compared with single lumpectomy) and increased body mass index increased the odds of developing a POC. Analyses of the ≥71-year group separately revealed only type of surgery to be of influence. Conclusions Fear of increased risk of complications in the older patient is unjustified. Neither increased age nor high American Society of Anesthesiologists classification are predictors for developing POC. Type of surgery is the most important determinant. Choosing mastectomy while breast-conserving surgery is suitable should be discouraged, particularly in the older patient.