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Combined Risk Assessment Prompts Treatment De-Escalation

Goodwin, Peter M.

doi: 10.1097/01.COT.0000534143.07968.12
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BARCELONA—Not only was breast-conserving therapy safer than mastectomy for most patients in the large randomized EORTC 10041/BIG 03-04 MINDACT trial reported at the 2018 European Breast Cancer Conference, but also the findings implied many patients could be advised to avoid chemotherapy and radiotherapy altogether after confirming their recurrence risks were low by using a combination of clinical and genetic scores (Abstract 2).

Emiel J.T. Rutgers MD, PhD, FRCS, a surgeon at the Netherlands Cancer Institute and Professor of Surgical Oncology at the University of Amsterdam, said MINDACT found a 5-year loco-regional recurrence (LRR) rate of only 2.1 percent in patients treated conservatively and only 2.5 percent in those who had mastectomy. Tumor size and grade were the only independent risk factors and the results provided “the opportunity to prospectively study de-escalation of radiotherapy in women with low-risk early breast cancer.”

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De-Escalation Trials

“Take this thorough information from MINDACT on board and do prospective studies where you omit radiotherapy in selected patients—that's the message,” Rutgers told clinicians. And he urged them to avoid recommending too many patients to have mastectomy. “Don't be afraid of breast conservation. There is now almost a tsunami of mastectomies. Women ask for mastectomies because they all believe it's better if the breast is off—which is not true. They are not better without their breasts,” he told Oncology Times.

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Recurrence Rates Low

The MINDACT researchers noted that LRR rates for breast cancer had decreased substantially over the past few decades. And since the 70-gene signature (70-GS) score had been found to improve risk prediction for distant metastases, it had already become easier to select patients in whom adjuvant chemotherapy could safely be omitted. The MINDACT study found evidence that combining a range of scores—including the 70-GS—made it possible think about investigating whether patients at low risk of relapse could avoid both radiotherapy and chemotherapy.

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Study Details

A total of 6,693 patients were enrolled of whom 5,470 (82%) chose conservative surgery and 1,223 (18%) opted for mastectomy. Most conservatively treated patients (98% of them) had adjuvant radiotherapy, while only 29 percent of those in the mastectomy group did.

Only 155 patients had recurrences within 5 years (120 in the breast-conserving therapy arm of the study and 35 in the mastectomy arm). Eighty-two patients had local relapses. In another 49, the recurrences were regional and a further 24 patients had both local and regional relapses.

Nine out of 13 variables—including genomic risk—were found individually to be associated with LRR with a highly significant p-value—less than 0.0001—and a hazard ratio of 2.5. In the final multivariate analysis (adjusted for treatment covariates in the breast-conserving therapy group), tumor grade and size remained significantly independently associated with LRR, while genomic risk did not.

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Studies Needed

This all added up to a ringing endorsement of a policy encouraging trials of gentler therapies from now. “These findings show that breast conservation is as good as mastectomy for selected women. And the risk of relapse is so low that we should look for ways of giving them less-aggressive treatment,” said Rutgers.

He suggested that even though radiotherapy halved the risk of LRR, it might still be avoided safely in patients with low risk scores and in some women aged over 50 with small tumors—less than 2 cm in diameter.

“The importance of this MINDACT analysis is that local and regional control—in which breast cancer does not come back in the preserved breast or in the skin or in the surrounding lymph nodes—is extremely good. The odds of the cancer coming back are about 2 percent in 5 years after breast conservation and 2.5 percent after mastectomy. This includes relapses in the surrounding lymph nodes.”

Rutgers said this very low risk was determined by the biology of the primary cancer including its grade, size, and growth pattern and by the patient's age—women over 50 having lower overall risk. “Among women aged over 50, those with slow-growing breast cancers have a 0.88 percent risk, and those with more aggressive ones have a 3.5 percent risk at 5 years,” he said.

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Lumpectomy as Good

“Another important message from these findings is that well-performed breast-conserving surgery in women with good indications is as good as mastectomy,” he said. “Doing a mastectomy when you could very well perform breast conservation will not add a day to the life of a breast cancer survivor.”

Rutgers was convinced MINDACT was “a wonderful trial that provided opportunities for further research.” And he urged that a prospective study should be performed to investigate whether women at low risk of a recurrence could avoid radiotherapy.

The conference chairperson, Robert E. Mansel, MS, FRCS, Emeritus Professor of Surgery at Cardiff University School of Medicine, U.K.—who was not involved with the study—noted: “These latest results from the MINDACT trial show the benefits to patients of large, international trials that have the power to detect whether or not it is possible to treat some women safely with less-aggressive therapies. Professor Rutgers and colleagues have shown that there is a group of patients who are at low risk of loco-regional recurrence and might be able to avoid radiotherapy and chemotherapy and the associated adverse side effects. I support his suggestion of a prospective trial to investigate this further in older [and] low-risk women.”

Peter M. Goodwin is a contributing writer.

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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