Efficacy and safety of endocrine therapy after mastectomy in patients with hormone receptor positive breast ductal carcinoma in situ: Retrospective cohort study
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eLife assessment
This valuable study describes the effects of endocrine therapy in a large series of Chinese patients treated with mastectomy (both efficacy and side effects). Whilst there are some caveats regarding the methodology (retrospective, small numbers of events, and some potential methodological bias in data collection) this is a solid piece of work and with further, ideally prospective data collection, has the potential to improve the management of patients with DCIS.
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Abstract
More than half of Chinese patients with hormone receptor positive (HR+) ductal carcinoma in situ (DCIS) are treated with mastectomy, and usually subjected to postoperative endocrine therapy (ET). Given that long-term ET can cause severe adverse effects it is important to determine the beneficial effect and safety of post-mastectomy ET on the disease-free survival (DFS) and adverse events in patients with HR+ DCIS.
Methods:
To explore beneficial effect and safety of post-mastectomy ET in patients with HR+ DCIS, we performed a multicenter, population-based study. This retrospective study analyzed the DFS and adverse events in 1037 HR+ DCIS Chinese patients with or without post-mastectomy ET from eight breast centers between 2006 and 2016. The median follow-up time period was 86 months.
Results:
There were 791 DCIS patients receiving ET (ET group). Those patients were followed up for a median of 86 months (range, 60–177 months). There were 23 cases with tumor recurrence or distant metastasis. There were similar 5-year DFS rates and DFS between the ET and non-ET groups, even for those with high-risk factors. Conversely, 37.04% of patients suffered from adverse events after ET, which were significantly higher than those in the non-ET group.
Conclusions:
ET after mastectomy did not benefit patients with HR+ DCIS for their DFS, rather increased adverse events in those patients. Therefore, ET after mastectomy may not be recommended for patients with HR+ DCIS, even for those with high-risk factors, such as multifocal, microinvasive, and higher T stage.
Funding:
This study was supported by grants from Outstanding Scientific Fund of Shengjing Hospital (201803) and Outstanding Young Scholars of Liaoning Province (2019-YQ-10).
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eLife assessment
This valuable study describes the effects of endocrine therapy in a large series of Chinese patients treated with mastectomy (both efficacy and side effects). Whilst there are some caveats regarding the methodology (retrospective, small numbers of events, and some potential methodological bias in data collection) this is a solid piece of work and with further, ideally prospective data collection, has the potential to improve the management of patients with DCIS.
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Reviewer #1 (Public Review):
In their paper "Efficacy and safety of endocrine therapy (ET) after mastectomy in patients with hormone receptor positive breast ductal carcinoma in situ: retrospective cohort study", Nan Niu et al describe the outcome of patients with DCIS treated by unilateral mastectomy with (n=791) and without (n=216) adjuvant endocrine therapy. This is a retrospective multicentre study with follow-up for at least 5 years.
Whilst this approach (ET post-mastectomy for DCIS) is rarely prescribed in the Western world (as the authors note) because the risk of recurrence of DCIS is very low (as shown in this series), some consider this appropriate for reducing the risk of contralateral breast cancer. This series of patients with unilateral mastectomy for DCIS thus provides more globally applicable information regarding the …
Reviewer #1 (Public Review):
In their paper "Efficacy and safety of endocrine therapy (ET) after mastectomy in patients with hormone receptor positive breast ductal carcinoma in situ: retrospective cohort study", Nan Niu et al describe the outcome of patients with DCIS treated by unilateral mastectomy with (n=791) and without (n=216) adjuvant endocrine therapy. This is a retrospective multicentre study with follow-up for at least 5 years.
Whilst this approach (ET post-mastectomy for DCIS) is rarely prescribed in the Western world (as the authors note) because the risk of recurrence of DCIS is very low (as shown in this series), some consider this appropriate for reducing the risk of contralateral breast cancer. This series of patients with unilateral mastectomy for DCIS thus provides more globally applicable information regarding the recommendation for adjuvant ET in the context of a potential reduction in contralateral cancer risk following a diagnosis of DCIS.
791 of the 1007 eligible patients received ET. The disease-free survival of patients in both groups was excellent, with no difference between those with and without ET. There was no difference in overall tumour recurrence, albeit with small numbers in both arms; 4 cases had invasive local recurrence (a comment confirming no radiotherapy had been received would be relevant), 3 had contralateral breast cancer and 12 had distant metastasis in the ET group while 4 cases with distant metastases were recorded in the non-ET group. Thus overall recurrence was low in both groups and the DFS was 98.36% vs. 99.07% between the ET and non-ET groups.
Conversely, adverse events (including fracture and endometrial cancer, but largely musculoskeletal) were seen in 37% of patients receiving ET. The grade of the adverse events is not reported so it is not possible to determine if these are mild or severe.
Strengths
This is a large and novel series of cases of DCIS, with detailed clinicopathological information.Weaknesses
The authors themselves note that this study is retrospective and with limited follow-up. The number of cases with recurrence is small, as would be expected. It would be important to note, as I presume, that none had radiotherapy.They have reported that they have included all hormone receptor positive cases. The definition of 'hormone receptor positive" has not been described in further detail, i.e. whether oestrogen and/or progesterone receptor and scoring system and cut-offs applied. It is presumed, therefore, that cases with any degree of receptor positivity are included. It is not apparent therefore whether there were any differences between those with low ER expression vs those with strong uniform reactivity.
All grades of DCIS were included. However, the % of cases (in both arms) with high-grade DCIS is surprisingly low (29% vs 24%); this is markedly different from what one sees, for example in the UK, where approx. 60% of all cases are of high histological grade. Conversely, the % of microinvasion reported is relatively high, particularly when considering the grade of the DCIS; it is well-recognised that microinvasion is much more common in association with high-grade DCIS. However, the Kaplan-Meier curve for disease-free survival of those with microinvasive carcinoma (Fig 2; D) is interesting and appears to show some separation (not significant presumably because of the small numbers not receiving ET).
Overall this is an interesting and thought-provoking manuscript highlighting the excellent outcome of patients with a wide range of DCIS lesions treated with unilateral mastectomy (whether they are in receipt of ET or not) and the high proportion of adverse events in those in receipt of adjuvant endocrine therapy.
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Reviewer #2 (Public Review):
The manuscript by Niu and colleagues reported that ET after mastectomy did not prolong the DFS of Chinese HR+ DCIS patients, but rather increased adverse effects. For the first time, the authors analyzed the beneficial effect and safety of ET after mastectomy in Chinese patients with HR+ DCIS through the clinical case review. The conclusion of this study is of great significance to guide the choice of appropriate treatment for Chinese patients with HR+ DCIS, and it has obvious benefits to reduce the economic burden of the patient's family and improve the quality of life for patients.
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Reviewer #3 (Public Review):
I agree with the authors that DCIS is a very common but understudied problem and longer-term follow-ups of cohort studies and randomized trials are needed.
I think the study described in this submission is a useful description of Chinese practice and patterns of care particularly with reference to the criteria that may have been used to select patients for endocrine therapy. It may also be of value for local and regional audits of care. Unfortunately, it does not help with any understanding of outcomes for the following reasons:
• It is retrospective in nature;
• The number of events is very small;
• The method of collecting information on side effects is not adequately described. I assume this is from case note review and ascertainment bias will therefore represent a major problem.It would be very …
Reviewer #3 (Public Review):
I agree with the authors that DCIS is a very common but understudied problem and longer-term follow-ups of cohort studies and randomized trials are needed.
I think the study described in this submission is a useful description of Chinese practice and patterns of care particularly with reference to the criteria that may have been used to select patients for endocrine therapy. It may also be of value for local and regional audits of care. Unfortunately, it does not help with any understanding of outcomes for the following reasons:
• It is retrospective in nature;
• The number of events is very small;
• The method of collecting information on side effects is not adequately described. I assume this is from case note review and ascertainment bias will therefore represent a major problem.It would be very misleading to assert causal relationships from this study.
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Reviewer #4 (Public Review):
This retrospective study addresses an important aspect of breast cancer treatment for prolonging survival and minimizing adverse events. Moreover, the findings could improve the treatment response of HR+ DCIS patients, which is very promising for the treatment. The article is mostly well-written and supported by encouraging data. The major strength of the study is the finding that ET after mastectomy should not be used for the treatment of HR+ DCIS patients. Nevertheless, only the Chinese population was analyzed, and that is the only limitation. This study would greatly help in the management of HR+ DCIS patients and in clinical decision-making.
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