Locoregional Treatment No Benefit For Chemotherapy-Responsive Metastatic Breast Cancer

Patients with de novo metastatic breast cancer who achieve a partial or complete response to first-line chemotherapy may avoid primary tumour treatment without jeopardising survival

medwireNews: Indian researchers challenge the routine use of locoregional treatment for metastatic breast cancer at diagnosis, on finding no overall survival benefit for patients who respond to front-line chemotherapy.

Overall survival was a median of 19.2 months in 173 women who were randomly assigned to receive surgery and/or radiotherapy compared with 20.5 months for the 177 patients who were not given locoregional treatment, with 2-year survival rates of 41.9% and 43.0%, respectively.

Rajendra Badwe and co-authors, from Tata Memorial Centre in Mumbai, emphasise that intention-to-treat analysis failed to find any survival benefit from treatment to the primary tumour and axillary lymph nodes for patient subgroups based on menopausal status, metastatic site and extent, or hormone receptor and HER2 status.

“Additionally, our data suggest that surgical treatment of the primary tumour in women with metastatic breast cancer cannot be justified on the grounds of achieving palliation and symptom control because only 18 (10%) of 177 women in the no locoregional treatment group required palliative surgery during follow-up”, they write in The Lancet Oncology.

Although locoregional treatment was associated with significantly improved locoregional progression-free survival compared with no locoregional treatment, it also conferred significantly poorer distant progression-free survival, with hazard ratios of 0.16 and 1.42, respectively.

“This finding is consistent with the results of preclinical studies, which showed growth of a metastatic tumour subsequent to the removal of the primary tumour”, the researchers observe, hypothesising that surgery may disseminate tumour cells into the circulation or induce immunosuppression or Angiogenesis.

David Cameron, from Western General Hospital in Edinburgh, UK, writing in a linked comment, queries the extent of metastatic disease that must be present before surgery does not improve patient survival, and whether this would include patients with 2 mm lesions detected by computed tomography, or those with distant disease on bone marrow biopsy or circulating tumour DNA.

“Indeed, as systemic therapy becomes more effective, it could be that subsets of patients without any macroscopic evidence of metastases, perhaps those achieving high pathological complete response rates after very active regimens, such as combination chemotherapy plus dual anti-HER2 therapy, could also gain little from surgery to the primary tumour”, he suggests.

The commentator concludes that study’s “clear evidence” against routine surgery in this patient population “leaves open two possibilities for future surgical practice changes for patients receiving very effective targeted therapy, if supported by additional, similarly high quality evidence: either additional surgery for those with detectable metastatic disease or perhaps even no surgery for those without.”

References

Badwe R, Hawaldar R, Nair N, et al. Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial. Lancet Oncol 2015; Advance online publication 9 September. DOI: http://dx.doi.org/10.1016/S1470-2045(15)00135-7

Cameron D. Removing the primary tumour in metastatic breast cancer. Lancet Oncol 2015; Advance online publication 9 September. DOI: http://dx.doi.org/10.1016/S1470-2045(15)00221-1

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