1. Lindsey, Heather

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Using a 70-gene expression score may allow oncologists to identify women with ultralow-risk breast cancer, meaning indolent tumors that pose an "exceedingly low" risk of death from breast cancer 20 years after diagnosis and treatment (JAMA Oncol 2017; doi:10.1001/jamaoncol.2017.1261). Women with ultralow-risk tumors could potentially be treated less aggressively with fewer side effects.

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In a statement, lead study author Laura J. Esserman, MD, Professor and Director of the University of California, San Francisco (UCSF) Carol Franc Buck Breast Care Center said: "This is an important step forward for personalizing care for women with breast cancer. We can now test small node-negative breast cancers, and if they are in the ultralow risk category, we can tell women that they are highly unlikely to die of their cancers and do not need aggressive treatment, including radiation after lumpectomy."


Overall, the study produced "rather compelling results," commented Dennis Holmes, MD, breast cancer surgeon, researcher, and Interim Director of the Margie Petersen Breast Center at John Wayne Cancer Institute at Providence Saint John's Health Center in Santa Monica, Calif. "For quite some time, oncologists have believed that many breast cancers are indolent and not life-limiting, but until now we haven't had convincing evidence that we could identify such cancers in individual patients."


Study Details

Investigators assessed data from the Stockholm breast cancer study group (STO)- low-risk trial that included 1,780 lymph-node-negative postmenopausal patients with tumors fewer than or equal to 3 cm in diameter, randomized to 2 years of adjuvant tamoxifen 40 mg daily versus no adjuvant treatment.


Using MammaPrint-which was developed by one of the study authors, UCSF cancer researcher Laura Van't Veer, PhD-the investigators profiled tumor tissue from 652 women, 311 of whom had received tamoxifen and 339 who had not. Seventy-nine percent of women had undergone mastectomy and lymph-node removal. All women had tumors detected in the era prior to the use of screening mammography.


The multigene test classified 42 percent of the patients as high-risk and 58 percent as low-risk. The investigators found that low-risk patients had a 95 percent survival rate at 5 years, but many later died from their disease.


The test classified 15 percent of the cases as ultralow risk, demonstrating that such tumors are an inherent part of the spectrum of breast cancers, even in the era before screening.


The women with ultralow risk tumors had an excellent prognosis, whether or not they used tamoxifen for 2 years, wrote the authors. Researchers reported no deaths in the ultralow-risk tamoxifen-treated arm at 15 years. These women also had a 20-year disease-specific survival rate of 97 percent. For patients who did not receive tamoxifen, the survival rate was 94 percent.


Personalized Treatment

"For every woman concerned about the impact of a breast cancer diagnosis on her long-term survival, the study provides extremely reassuring results that an ultralow-risk score is a predictor of excellent long-term survival," said Holmes. This study further illustrates that breast cancer is a spectrum of diseases for which there should be a range of personalized treatment options.


"This is extremely good news for breast cancer surgeons and researchers like myself who are committed to offering individualized breast cancer treatments based on a woman's personal risk of breast cancer recurrence," said Holmes. For example, women with an ultra-low risk score may be able to omit tamoxifen from their treatment regimen, noted Holmes. "The evidence supports that decision."


Ultralow-risk tumors could also benefit from innovative cancer treatments like cryoablation, which is currently being evaluated as an alternative to cancer surgery and radiation in the FROST Trial, a national clinical study chaired by Holmes. "In fact, we plan to integrate the Mammaprint test to select cryoablation candidates who may safely avoid lymph node surgery," he noted.


In addition to cryoablation, intraoperative radiotherapy administered in a single targeted dose at the time of surgery is another alternative to traditional 6-week postoperative radiation that Holmes offers to carefully-selected patients.


While aggressive treatment is often the fear-driven default approach, aggressive treatment of ultralow-risk tumors exposes women to the side effects and risks of treatment without similar offset in benefit, said Holmes. "More treatment does not necessarily mean more benefit, and sometimes it just means more risk," he added.


Screening Mammography Still Critical

Holmes noted that screening mammography is still critical for early detection of breast cancer in women, regardless of tumors being ultralow, moderate, or high risk. Practitioners need to keep in mind that only 15 percent of tumors were identified by the study as ultralow risk, which means the other 85 percent may need more aggressive treatment, especially if larger than 2 cm, he said.


Heather Lindsey is a contributing writer.