Breast‐conserving surgery followed by whole‐breast irradiation offers survival benefits over mastectomy without irradiation. BJS 2018; 105: 1607-1614.

Published: 21st June 2018

Authors: J. de Boniface, J. Frisell, L. Bergkvist, Y. Andersson

Background

The prognostic equivalence between mastectomy and breast‐conserving surgery (BCS) followed by radiotherapy was shown in pivotal trials conducted decades ago. Since then, detection and treatment of breast cancer have improved substantially and recent retrospective analyses point towards a survival benefit for less extensive breast surgery. Evidence for the association of such survival data with locoregional recurrence rates is largely lacking.

Method

The Swedish Multicentre Cohort Study prospectively included clinically node‐negative patients with breast cancer who had planned sentinel node biopsy between 2000 and 2004. Axillary lymph node dissection was undertaken only in patients with sentinel node metastases. For the present investigation, adjusted survival analyses were used to compare patients who underwent BCS and postoperative radiotherapy with those who received mastectomy without radiotherapy.

Results

Of 3518 patients in the Swedish Multicentre Cohort Study, 2767 were included in the present analysis; 2338 had BCS with postoperative radiotherapy and 429 had mastectomy without radiotherapy. Median follow‐up was 156 months. BCS followed by whole‐breast irradiation was superior to mastectomy without irradiation in terms of both overall survival (79·5 versus 64·3 per cent respectively at 13 years; P < 0·001) and breast cancer‐specific survival (90·5 versus 84·0 per cent at 13 years; P < 0·001). The local recurrence rate did not differ between the two groups. The axillary recurrence‐free survival rate at 13 years was significantly lower after mastectomy without irradiation (98·3 versus 96·2 per cent; P < 0·001).

Conclusion

The present data support the superiority of BCS with postoperative radiotherapy over mastectomy without radiotherapy. The axillary recurrence rate differed significantly, and could be one contributing factor in a complex explanatory model.

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2 Comments

Ramya Valiveru

11 months ago

In this article the authors have made a relevant comparison between the two surgical options of BCS+RT and mastectomy for early breast cancer patients from a prospective study (1).

There are significant differences between the two groups relating patients’ age, tumour characteristics including size, grade and focality, with unfavourable features represented more in the mastectomy group. Significantly higher proportions of patients in the BCS+RT group received cytotoxic therapy which could potentially confound the observed axillary recurrence rates and survival rates (2,3). Multi-focal tumours should have been excluded from analysis in the mastectomy group as well. Features like the lympho-vascular invasion, perineural invasion and extra-nodal extension which could possibly influence the recurrence rates (4) have not been taken into consideration. Currently, the pN1 stage is an indication for post-mastectomy chest-wall RT. Patients with N1 and N2 stages in the mastectomy group of this study were not administered RT, which would have possibly influenced the axillary recurrence rates. So, exclusion of pN1 and N2 patients from the analysis may provide a more valid comparison of recurrence rates in the axilla between the two groups. We agree with the conclusion that the type of surgery and addition of RT alone decreased the isolated axillary recurrence rates in BCS+RT group. Attributing better survival outcomes to these alone and that survival was not influenced by the other factors that we have highlighted above is not a valid conclusion to draw.

Ramya C Valiveru
Sabaretnam M
Gaurav Agarwal
Sanjay Gandhi

Post Graduate Institute of Medical Sciences
Lucknow
India
ramya.nageen@gmail.com

References:
1. de Boniface J, Frisell J, Bergkvist L, Andersson Y. Breast-conserving surgery followed by whole-breast irradiation offers survival benefits over mastectomy without irradiation. Br J Surg. 2018 Jun 21;
2. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. The Lancet. 2005 May 14;365(9472):1687–717.
3. Polychemotherapy for early breast cancer: an overview of the randomised trials. The Lancet. 1998 Sep 19;352(9132):930–42.
4. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. The Lancet. 2005 Dec 17;366(9503):2087–106.

    Jana de Boniface

    11 months ago

    We appreciate the comments by Mr. Valiveru and colleagues regarding the significant differences between the two studied groups, namely BCS+RT and mastectomy without RT. We agree that such differences complicate any comparison but wish to confirm that our results are nevertheless valid.

    Due to selection criteria for the procedure, mastectomy patients have larger tumours, a higher rate of multifocality and a larger proportion of lobular subtype. Interestingly, they also tend to have worse tumour biology and a higher rate of node positivity. As the present study is not based on randomised data, appropriate statistical measures to adjust for such differences have been applied. Notably, chemotherapy does have an effect on breast cancer-specific survival on univariable analysis, which is, however, lost when adjusting for tumour and patient characteristics. Unfortunately, LVI was unavailable in this historical cohort; it seems rather unlikely, however, that one single factor would reverse our findings.

    To assure our colleagues that conclusions are valid, we re-analyzed data removing multifocal cases and node-positive mastectomy patients not receiving RT (N=233). Results were not changed by this measure, confirming the multivariable regression analysis correctly adjusting for group differences; HR for breast cancer death for mastectomy patients remained significant at 1.41 (95% c.i. 1.13-1.77), while chemotherapy remained non-significant.

    Adding these results to the known positive effects of BCS on morbidity, quality of life and health care consumption, we maintain that BCS+RT should be the first choice for patients with tumours at least up to 3 cm in size, regardless of nodal metastases.

    Jana de Boniface
    Department of Molecular Medicine and Surgery
    Karolinska Institute
    Stockholm
    Sweden
    Jana.De-Boniface@ki.se