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Surgery Extends Survival of Metastatic Breast Cancer Patients

Laino, Charlene

doi: 10.1097/01.COT.0000363654.77679.a9
ECCO15-ESMO34 Joint Congress

BERLIN—Breast cancer patients with distant metastatic disease at diagnosis live about twice as long if the primary tumor is surgically removed, a large retrospective study suggests.

“Three to 10 percent of patients with breast cancer have distant metastases at presentation, which means that within months of being diagnosed with primary tumor, they will also be diagnosed with metastatic disease,” said Jetske Ruiterkamp, MD, a surgical resident at Jeroen Bosch Hospital in Den Bosch, The Netherlands.

“Their median survival time is only one to two years, and treatment is focused on maintaining or improving their quality of life,” she said here at the joint Congress of the European CanCer Organisation and European Society for Medical Oncology.

Although historically, only patients with symptomatic primary tumors were offered local treatment for metastatic breast cancer, some recent studies have suggested that removal of the primary tumor may increase survival, Dr. Ruiterkamp explained.

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Median Survival 31 Months in Resected Patients

To determine the impact of surgery on the survival time of patients with metastatic breast cancer, the researchers reviewed the medical records of 728 patients who had distant metastases at diagnosis. Forty percent of them had surgical resection of the primary breast tumor.

The median survival was 31 months in women who had surgery, compared with only 14 months for those who did not. The five-year survival rate was 24.5% in the group who had surgery vs 13% in those who did not.

In a multivariate analysis adjusted for age, period of diagnosis, the number of metastatic sites, and different types of treatment, surgery reduced the risk of death by 38%. Compared with patients who did not have surgery, surgically treated patients were younger, less likely to have more than one metastasis, less likely to have comorbid conditions, and more likely to receive radiation therapy or systemic therapy.

“Surgery is an independent prognostic factor for overall survival in patients with metastatic breast cancer,” she concluded.

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Will the Findings Change Practice?

Dr. Ruiterkamp called for a randomized, controlled trial to verify the findings.

In response to a question from the audience, she said the most likely explanation for the better survival rates in the surgically resected patients is “that by excising the primary tumor, we reduce the number of circulating tumor cells in the body. It is also possible that surgery reactivates the immune system.”

ESMO President José Baselga, MD, Chairman of the Medical Oncology Service at Vall d'Hebron University Hospital in Barcelona, agreed. “Experimental models suggest that the primary tumor is a reservoir for self-seeding cancer stem cells” that fuel the cancer's growth and spread. There's a biological reason to believe that local control improves survival,” he said.

And although there are now a number of studies suggesting that surgery can extend survival for late-stage breast cancer patients, he said that until the results are confirmed in a randomized controlled trial, he doubted the findings will change practice.

Still, “patients may ask about the surgery, so oncologists should be aware of the findings,” Dr. Baselga said.

Dr. Ruiterkamp said that the researchers are currently analyzing further information about the patients to find out how they were diagnosed—whether by screening or because they had symptoms, for example. The group is also looking at the type of surgery and the impact of tumor-free resection margins.

“We hope this will give us better insight into the subset of patients who would benefit most from surgical excision,” she said.

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Methotrexate Found to Selectively Destroy Faulty MSH2 Gene

Methotrexate can selectively destroy cells containing the faulty MSH2 gene linked to bowel and other cancers, according to a study published in EMBO Molecular Medicine.

Researchers from the Breakthrough Breast Cancer Research Centre at the Institute of Cancer Research (ICR) in London tested a range of agents with the goal of improving treatment for people with hereditary nonpolyposis colorectal cancer, about 40% of whom have a faulty MSH2 gene.

In looking for drugs that could selectively kill cells containing that, the researchers found that that was the case for methotrexate, which appeared to work particularly well in destroying those cells, thus opening up the possibility of a more targeted option for people whose cancer is driven by the MSH2 genetic fault.

As explained in a news release, methotrexate is similar to folinic acid, which is required for copying DNA. The drug prevents cells from making and repairing DNA, but although invented in the 1940s and used to treat several cancers, has until now generally not been used for HNPCC.

A new clinical trial of the use of methotrexate in HNPCC patients has now begun at Royal Marsden NHS Foundation Trust.

“The MSH2 gene plays a vital role in repairing DNA damage but if it is faulty, mistakes accumulate in cells and increase the risk of cancer developing,” said Professor Alan Ashworth, who led the ICR study. “What's exciting about methotrexate is that it selectively destroys the cells lacking the MSH2 function. This indicates that it may make an excellent treatment for patients with the genetic alteration. With our colleagues at the Royal Marsden Hospital, we have set up clinical trials to test this.”

© 2009 Lippincott Williams & Wilkins, Inc.
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