1. Goodwin, Peter M.

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TURIN, Italy-Younger women with low-risk early breast cancer treated with mastectomy had lower mortality than those receiving breast-conserving therapy (BCT) after 20 years of follow up in a large Danish study reported at ESTRO 2016-the annual meeting of the European Society for Radiotherapy and Oncology.

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The study looked at the long-term age-dependent failure pattern after BCT as compared with mastectomy in patients with low-risk breast cancer and was begun before the time when adjuvant systemic therapy became an option for this group. For this reason the higher risk of conservative therapy found among women younger than 45 years now needs to be assessed in the context of current practice, said lead author Tinne Laurberg, MD, a pathologist from the Department of Experimental Clinical Oncology at Aarhus University Hospital in Denmark (Abstract: E35-1485).


Nevertheless she said there was a clear finding: "I can only say that if young patients having breast-conserving therapy have not had adjuvant systemic treatment they have a higher risk of distal metastases, and all-cause mortality compared to compared to [patients who had] mastectomy," she told Oncology Times.


Study Findings

Laurberg said her group's study was unusual because of the high number of young women recruited-including all 301 Danish patients under 41 diagnosed from 1989 to 1998. Prior studies comparing BCT with mastectomy had low proportions of younger patients making it harder to reach statistically significant conclusions. Altogether, 1076 Danish women diagnosed with breast cancer were followed for up to 20 years. All were classified as low risk because they have tumor diameters less than five centimeters and no nodal involvement. 364 women had BCT while 712 had mastectomy. None of the patients received systemic therapy.


Laurberg said they wanted to see how long-term outcome varied with treatment among low-risk patients-especially young ones. "Because we know that this group has a higher local recurrence rate and we wanted to see if this translated into a higher mortality," she explained.


After 20 years 18 percent of women treated with BCT had local recurrences as compared with only 6.7 percent of those given mastectomy. Additionally the study found that most recurrences occurred within 5 years among women treated with mastectomy as compared with 10 years for those having BCT (who continued to have recurrences throughout the 20 year follow up).


Laurberg said local recurrence was not associated with distant metastasis in women older than 45 but was strongly related to it in younger women. And there was no therapy-related difference in 20-year mortality for this older group.


But in women younger than 45 local recurrence was associated with distant metastasis and those who had BCT had an increased risk of death from all causes during the 20 years following their diagnosis compared with the mastectomy-treated patients.


Laurberg said the possibility of a negative impact of BCT should be taken into account in the future when choosing treatment for young women. "We find a very distinct pattern. Patients below 45 years had a higher local recurrence rate compared to the older ones. And more interestingly, they have a 2.7 higher risk of getting distant metastases than the ones having mastectomy," she noted.


Study Recommendations

When she was asked about possible recommendations coming out of the study findings Laurberg agreed BCT was safe for older women. "With "old" defined as 45 years! Normally you won't think that a person [of] 46 is an older woman-so it's very important to have it in this context," she said.


Sofia Riviera, Head of the Breast Cancer Unit in the Department of Radiation Therapy at the Institut Gustave Roussy, in Paris commented that in younger patients it might make a difference to have a mastectomy rather than breast-conserving surgery plus radiotherapy.


She told Oncology Times that with older data showing no difference in survival it was noteworthy that this new study with large numbers of young women had found a difference. "What we can see is that-specifically for these younger patients-we have a difference."


Nevertheless, Riviera kept an open mind. "We have to be very cautious because although there was a large number of young patients with long overall survival and more than 17 years of follow-up there was no systemic treatment," she said, adding that nowadays similar patients might have systemic treatment that could be a confounding factor.


When asked what recommendations she would make if a young woman came into her office who was node negative and had a tumor less than five centimeters Riviera said it depended on the characteristic of the tumor and factors like HER2 status that were not reflected in the trial presented by Laurberg. "She had a very small number of patients [with] HER2 over-expressed. So typically for that kind of patient I [would] look into the genetic profile, and probably propose a test with a signature to orientate my strategy in choosing whether [to] do systemic treatment or not," she said.


But did she think there should now be a resurgence of interest in mastectomy for young women with low-risk disease?


Riviera wouldn't say. "Mastectomy is very invasive, especially for young women. I would be very cautious and confirm that [these new findings] with a trial in which systemic treatment is evaluated," she said.


President of ESTRO, Philip Poortmans, MD, PhD, Professor of Radiation Oncology at Radboud University in Nijmegen, Netherlands, who was not involved in the research, commented that this study highlighted the importance of obtaining and maintaining optimal local tumor control since local recurrences appear to be a source for development of subsequent distant metastases.


"We have to view this from the right perspective, though, as we have witnessed a remarkable decrease in the rate of local recurrences after BCT, even for young patients. On the other hand, these results might also be a warning signal about the possible risks associated with the recent trend towards the use of less aggressive breast cancer treatments -particularly those aimed at the area of the primary tumor," he said.


When Riviera was asked about recommendations, she said the trial doesn't yet change these. "It just raises some new questions, brings some new data that point out the fact that in this specific sub-group of patients-that are younger than 45 years-we should reconsider the options. And we should design specific trials for that," she concluded.


Peter M. Goodwin is a contributing writer.