Mode of Detection of High-Risk Breast Cancer Linked to Prognosis

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Breast cancers detected between mammographic screenings carry a worse prognosis than those detected at the time of screening, even when tumor biology is similar, according to research presented at the 12th European Breast Cancer Conference (EBCC 12), which was held virtually this year.1

The 8-year distant metastasis–free interval rate was higher among women with screen-detected cancers than in those with interval cancers: 93.8% vs 85.2%. When these tumors had high-risk biology, patients with screen-detected tumors still fared better, said Josephine Lopes Cardozo, MD, a doctoral candidate at The Netherlands Cancer Institute, Amsterdam, and a medical fellow at the European Organisation for Research and Treatment of Cancer.

Josephine Lopes Cardozo, MD

Josephine Lopes Cardozo, MD

“Although these tumors have the same biology—all 70-gene, high-risk, and with similar tumor characteristics—they have different prognoses based on their method of detection. This suggests the method of detection is an additional prognostic factor,” she said.

Dutch Screening Program Linked to MINDACT

The study used data from the long-term follow-up of the MINDACT trial—specifically, distant metastasis–free interval as determined after a median of 8.7 years of follow-up. The updated, long-term analysis of MINDACT was also presented at EBCC 12 by Rutgers et al.2

Dr. Lopes Cardozo and colleagues looked at all Dutch patients with breast cancer enrolled in MINDACT between 2007 and 2011 who were also participants in the Dutch national screening program (biennial screening for women aged 50 to 75 years). For this population of 1,102 patients, they evaluated differences in distant metastasis–free interval for tumors with high-, low-, and ultra–low-risk biology according to the 70-gene expression profile (MammaPrint) used in MINDACT. The threshold for “ultra–low risk” was set at an index of 0.7, representing “indolent” breast cancer that has been found to have a 100% breast cancer–specific survival at 15 years.

The study aimed to evaluate the association between tumor biology and distant metastasis–free interval (the time from diagnosis to first distant metastasis or breast cancer–related death) for screen-detected and interval cancers. Screen-detected cancers were those that were mammographically identified in the first or subsequent screening round. Interval cancers were symptomatic breast cancers diagnosed within 24 and 30 months after a negative mammographic exam.

More screen-detected vs interval cancers were low risk (69% vs 52%), more interval cancers were high risk (48% vs 31%), and a similar proportion (21%) were ultra–low risk. The screen-detected cancers were more likely to be smaller, of lower grade, and estrogen receptor–positive. As expected, adjuvant systemic treatment was more common among the 70-gene, high-risk patients, whether detected during or between screenings. High-risk patients received more chemotherapy than the low-risk and ultra–low-risk patients in either cohort, and this occurred more often with the interval cancers.

Distant Metastasis–Free Interval

After a median follow-up of 8.7 years, there were 83 occurrences of distant metastases or deaths due to breast cancer. Among screen-detected cancers, distant metastasis–free interval rates were similar and “excellent” for all the 70-gene risk groups, but for interval cancers, there were significant differences among these groups. The differences in distant metastasis–free interval between screen-detected and interval cancers were notable for patients in the high-risk category.

Within the high-risk group, after the investigators adjusted for clinical risk status and adjuvant systemic therapy, the hazard ratio for developing distant metastasis was 2.4 for interval vs screen-detected cancers. This difference was not observed in the low-risk and ultra–low-risk groups.

Dr. Lopes Cardozo summarized the study’s key findings with the following points: (1) screen-detected cancers more often have a low-risk or ultra–low-risk tumor biology according to the 70-gene signature; (2) screen-detected cancers are associated with a better 8-year distant metastasis–free interval vs interval cancers; (3) within the high-risk biology group, the prognosis of screen-detected cancers is significantly better than that of interval cancers.

“The method of detection is an additional prognostic factor in the 70-gene signature high-risk subgroup and should be taken into account when deciding on adjuvant treatment strategies,” she advised. However, she cautioned, the results of this study should be confirmed in another series. 

DISCLOSURE: Dr. Lopes Cardozo reported no conflicts of interest.


1. Cardozo JL, et al:Screen-detected breast cancers have different tumour biology and better prognosis compared to interval breast cancers. 12th European Breast Cancer Conference. Abstract 11. Presented October 3, 2020.

2. Rutgers E, et al: MINDACT: Long-term results of the large prospective trial testing the 70-gene signature MammaPrint as guidance for adjuvant chemotherapy in breast cancer patients. 12th European Breast Cancer Conference. Abstract 21. Presented October 3, 2020.

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