Management and 5-year outcomes in 9938 women with screen-detected ductal carcinoma in situ: the UK Sloane Project

TL;DR: Recurrent DCIS or invasive cancer is uncommon after screen-detected DCIS and both RT and endocrine therapy were associated with a reduction in further events but not with breast cancer mortality within 5 years of diagnosis.

About: This article is published in European Journal of Cancer.The article was published on 2018-08-06 and is currently open access. It has received 46 citations till now. The article focuses on the topics: Breast cancer & Breast-conserving surgery.

Summary

Introduction

• Of breast screening and now comprises 20-25% of screen-detected breast cancer.
• Like invasive breast cancer, DCIS is heterogeneous in terms of underlying biology, presentation and outcome [2].
• The clinical behaviour of DCIS is unpredictable, challenging clinical decision-making.
• Recently, concern regarding the over-treatment of DCIS [2], has been fueled by large retrospective American series demonstrating excellent (>95%) long term survival 10-20 years after diagnosis although others have suggested that detection and treatment of screendetected DCIS may prevent subsequent invasive disease. [3-5].
• It remains unclear which patients benefit from these adjuvant therapies.

Methods

• The United Kingdom National Health Service Breast Screening Programme invites women aged 50-70 to attend breast screening every three years .
• The data reported here is for women in the dataset who had DCIS identified.
• Radiology guidelines mandated participating radiologists should complete detailed radiology proformas [10] and participate in the NHSBSP PERFORMS external quality assurance scheme. [11].
• Events were identified by matching women by NHS number and date of birth to information provided by breast screening units, and to routinely collected UK datasets including Hospital Episode Statistics (HES), Cancer Waiting Times (CWT), the English Cancer Analysis System (CAS)/National Cancer Registration and Analysis Service , the English National Radiotherapy Dataset (RTDS) and the Information Services Division, Scotland (ISD).

Classification of recurrence & mortality

• Given the difficulties in distinguishing local recurrence versus a new primary lesion in the same breast, the following terminology was used .
• A ‘breast event’ was defined as (any of): ipsilateral breast recurrence (or new primary) after BCS; ipsilateral 6 recurrence (includes post-mastectomy/chest wall recurrence); regional or distant recurrence; or contralateral re/occurrence.

Statistical analyses

• Logistic linear regression analysis was used to test the relationship between a binary variable and continuous or ordered categorical dependent variables.
• A factor with a lower p-value from the likelihood ratio test was deemed to be more important than one with a higher p-value.
• K-sample tests were performed to compare the groups in the cumulative incidence plots.
• Tied times were adjusted using the Breslow’s method.
• The proportional hazard assumption was assessed by Schoenfeld residuals test.

Patterns of care

• Seventy-eight breast screening units in England and Scotland contributed data (82% of the 95 units).
• Over the same decade in the UK, 30,187 women were diagnosed with non-invasive and microinvasive breast cancers through the NHSBSP; thus, the data analysed represent 77% (9938/12,838) of non-invasive lesions within this prospective cohort, and 33% (9938/30,187) of women with a final diagnosis of in situ breast carcinoma diagnosed through the NHSBSP.

Surgical treatment

• Breast conservation surgery (BCS) was definitive surgery in 7007 (70%) women and was utilised more often with increasing age up to 59 years and thereafter appeared constant.
• The use of mastectomy was associated with DCIS of high or intermediate rather than low grade (p<0.001) and with larger lesion size (p<0.001).
• The use of BCS versus mastectomy was unchanged over time.

Endocrine Therapy

• The use of endocrine therapy was not related to age and was prescribed less frequently over time (p<0.001).
• There was no relationship between the receipt of endocrine therapy and RT use after BCS.

Survival

• The use of endocrine therapy was not associated with overall or breast cancer specific mortality.
• Women who developed an invasive breast recurrence had a significantly worse overall survival (log rank p-value <0.001) and breast cancer specific survival (log rank p-value<0.001) from the time of the further event compared with those who developed recurrent DCIS .

Discussion

• This study of 9938 women with DCIS detected through the UK NHSBSP confirms that recurrent DCIS or invasive cancer remains a concern following modern management of screen-detected DCIS.
• The present prospective cohort study contrasts with recent but retrospective studies of US [3, 4] and European data. [13].
• Whilst it is likely that RT following BCS was used in patients perceived (based on 10 pathological and patient-related factors) to be at higher risk of recurrence, RT use was, surprisingly, not associated with close or involved circumferential resection margins.
• Nevertheless, patients not receiving RT had a higher (7.2%) breast recurrence rate, confirming patient selection for RT could be improved. [23].
• This requires a greater understanding of the underlying biology of DCIS, on reliable predictive and prognostic assessment, particularly to select women at risk of invasive breast cancer recurrence.

Conclusions

• This large prospective cohort study allows us to examine, in contemporary practice, the effects of present-day treatments, and the patient and pathological features that have previously been described in retrospective studies and randomised clinical trials.
• The reduction in recurrence rates seen with the use of RT and endocrine therapy has not, to date, yielded a survival benefit to patients, although other-cause mortality is five times greater than that attributable to breast cancer.
• Ipsilateral breast recurrence risk is, however, higher in patients treated by BCS without RT, particularly if the radial excision margin is narrow (<2mm).
• Women with recurrence as invasive disease have poorer survival than those with recurrent DCIS and further research targeting clinical, biological and imaging 12 biomarkers of risk of invasive recurrence after a diagnosis of screen-detected DCIS is indicated, to improve personalisation of therapy and outcomes.

Figures

Figure 1: 9938 UK patients with screen-detected DCIS (2003-2012).

Figure 3: Survival from the date of recurrence

Figure 2: Radiotherapy (RT) and ipsilateral breast events.

Table 1: Radiotherapy (RT) use & pathological features after breast conservation surgery (BCS).

Frequently asked questions

Q1. What was the effect of RT on ipsilateral recurrence?

Adjuvant endocrine therapy (1208/9938; 12%) was associated with a reduction in any ipsilateral recurrence, whether RT was received (HR 0.57: 95% CI 0.41 - 0.80) or not (HR 0.68: 95% CI 0.51 - 0.91) after BCS. 

Q2. What was the risk of a breast recurrence after BCS?

Ipsilateral breast recurrence after BCS was 5.3% (368/7007); ipsilateral chest wall recurrence after mastectomy was 0.8% (24/2931). 

Q3. What was the effect of RT on breast recurrence?

Endocrine therapy was associated with a non-significant reduction in ipsilateral breast recurrence independent of RT, although the greatest effect was seen for the reduction of invasive further events in the absence of RT. 

Q4. What were the requirements for participating units?

Participating units were required to follow a pathology protocol containing definitions for DCIS, microinvasion, cytonuclear grade, comedo necrosis and assessment of excision margins and to handle and report specimens to NHSBSP pathology standards. [8] 

Q5. How many women are invited to breast screening every three years?

The United Kingdom National Health Service Breast Screening Programme (NHSBSP) invites women aged 50-70 to attend breast screening every three years (supplementary figure and text p2). 

Q6. What was the association of RT with breast recurrence?

mastectomy was, not unexpectedly, associated with features of more aggressive DCIS.RT following BCS was associated with a significant reduction in all ipsilateral breast further events (DCIS or invasive) at a median follow up of 64 months. 

Q7. What is the impact of digital mammography on breast cancer?

12]The increasing incidence of DCIS, likely to be sustained with the enhanced visualisation that digital mammography provides, now deployed in the UK NHS BSP, emphasises the potential for overtreatment of women diagnosed though breast screening. [1] 

Q8. What was the requirement for participating radiologists to complete a radiology proforma?

Radiology guidelines mandated participating radiologists should complete detailed radiology proformas [9] and participate in the NHSBSP PERFORMS external quality assurance scheme. [10] 

Q9. What was the association between mastectomy and breast cancer?

The use of mastectomy was associated with DCIS of high or intermediate rather than low grade (p<0.001) and with larger lesion size (p<0.001).