Surgery not beneficial in de novo stage IV breast cancer

By Mardi Chapman

2 Jun 2020

Associate Professor Prue Francis

Adding in locoregional treatment (LRT) to optimal systemic treatment does not improve overall survival in women who present with de novo stage IV breast cancer and an intact primary tumour.

Professor Seema Khan, a breast cancer surgeon from Northwestern Medicine in Chicago, presented the findings of the ECOG-ACRIN study 2108 to the ASCO20 Virtual Scientific Program.

The 390 patients received optimal systemic therapy for their disease over 4-8 months and after no disease progression were randomised to local tumour resection and radiotherapy or continued systemic therapy alone.

More than half the women (54%) had HR positive and HER2 negative breast cancer, 29% had HER2 positive and 10% had triple negative disease. Metastatic sites included bone (31.5%), viscera only (26.4%) or both (27.2%).

Initial systemic therapy included chemotherapy with or without a HER2 directed therapy (54%), only endocrine therapy (27%), or both endocrine and chemotherapy (14%).

The study found 3-year overall survival was similar in both groups (68.4% v 67.9%; p=0.63). Progression free survival was also similar in both groups (p=0.4)

A subgroup analysis found women with triple negative breast cancer appeared to do significantly worse with early local therapy while women with other tumour subtypes had no difference in survival based on the treatment they received.

The study also found that health-related quality of life was similar in both groups at most time points but worse in the patients receiving early local therapy at 18 months.

“Although we saw a 2.5 fold higher risk of local disease progression without LRT, the use of LRT for the primary site did not lead to improved HRQOL,” the meeting was told.

The researchers concluded that locoregional therapy should not be offered to women with stage IV breast cancer with the expectation of a survival benefit.

“When systemic disease is well controlled with systemic therapy but the primary site is progressing, LRT may be considered.”

Commenting on the study, Australian Associate Professor Prue Francis told the limbic the findings would certainly inform discussions about treatment options in the distressing situation of de novo stage IV disease.

“I think it is a helpful study because, particularly if a surgeon has been talking about surgery, then investigations come back showing distant metastases, it helps explain why they are now not recommending surgery.”

“That’s not to say that no patients with metastatic disease will ever get surgery in the future.”

She said there might be individual cases where a patient has a single distant metastasis.

“In that scenario, without there being a clear RCT to show this is better, sometimes they will treat more along the lines of removing the primary but also doing some sort of local ablative therapy to that oligometastasis.”

Associate Professor Francis said there were other cancers where previous data have suggested a survival advantage from removing the primary tumour even if there were distant metastases.

“For example, it’s quite common to de-bulk ovarian cancers with sometimes quite substantial surgery even if there might be quite distant spread.”

“And going back a few years there was data in kidney cancer that even if patients had distant spread there seems to be some advantage in removing a primary.”

“In breast cancer we didn’t have very good randomised trials,” she said.

“I think this study is certainly very helpful because historically there were mainly retrospective series. The importance of this plenary presentation was to obtain objective data because one of the concerns with all those retrospective publications was they were potentially subject to bias.”

“I don’t think this study can say that no patients with stage IV disease should have surgery but certainly it needs to be very carefully thought about.”

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