In December 2025, results from the LORETTA trial were presented at the San Antonio Breast Cancer Symposium (SABCS), offering new insight into an important and long-standing question in DCIS care: Can some people with low-risk DCIS safely avoid surgery?
While the trial did not meet its predefined statistical threshold, the findings add meaningful evidence to the growing body of research suggesting that active surveillance may be appropriate for carefully selected patients. Importantly, the results help clarify who those patients might be.
What Was the LORETTA Trial Studying?
The LORETTA trial (JCOG1505) evaluated tamoxifen alone, without upfront surgery, in women with strictly defined low-risk DCIS. All participants had estrogen receptor–positive, HER2-negative DCIS, no signs of invasion on advanced imaging, and relatively small tumors.
Rather than comparing surgery to no surgery, LORETTA was designed as a confirmatory single-arm study, asking whether outcomes with endocrine therapy alone stayed within a conservative safety boundary set by the researchers before the trial began.
The Headline Result — and Why Context Matters
At five years, the cumulative incidence of invasive cancer in the same breast was 9.8%. Because this percentage exceeded the study’s prespecified 7% threshold, the trial technically did not meet its primary endpoint and early termination was recommended.
However, this does not mean that tamoxifen-only management was shown to be unsafe.
That 7% cutoff was a research benchmark, not a biological tipping point. It was intentionally cautious, reflecting how early the field still is in formally studying non-surgical approaches for DCIS.
In real-world terms:
- More than 90% of participants did not develop invasive cancer at 5 years
- Overall survival was nearly 99% and no breast cancer-related deaths were reported.
- Fewer than 1 in 10 participants ultimately went on to surgery
- Serious side effects were uncommon
These outcomes are particularly notable given that all participants avoided immediate surgery.
A Reassuring Signal: Imaging May Help Identify the Best Candidates
One of the most encouraging findings from LORETTA was where risk appeared to concentrate.
The likelihood of developing invasive cancer was associated with tumor size on imaging (mammogram, ultrasound, and MRI), rather than traditional pathological features like nuclear grade or hormone receptor strength.
This suggests that DCIS behavior may be better predicted by how it presents on imaging than by microscopic features alone—a key insight for refining future active surveillance strategies.
Expert Interpretation: Progress, Not Failure
When the LORETTA results were discussed at SABCS, an important theme emerged from experts like Eric P. Winer, Director of the Yale Cancer Center. In a recent HealthDay TV segment highlighting the trial results, he emphasized that while the rate of recurrence was higher than expected, the actual number of invasive cancers remained relatively low at five years, especially considering that all participants avoided immediate surgery.
Watch Dr. Winer’s interpretation here:
👉 Is tamoxifen alone a viable option for women with low-risk DCIS breast cancer?
Dr. Winer’s perspective underscores a hopeful point: a technically “negative” trial can still yield clinically meaningful insights. Rather than seeing LORETTA as a dead end for active surveillance, he framed it as evidence that some women with low-risk DCIS may indeed do well with less aggressive management, provided they are chosen carefully and monitored closely.
This interpretation aligns with other expert commentary at SABCS — that the study helps clarify who might be a good candidate for non-surgical approaches, rather than serving as a blanket verdict against them.
What This Means for Patients Today
Surgery remains the standard recommendation for DCIS, and LORETTA does not change clinical guidelines on its own.
But the study reinforces an important message: DCIS is not one-size-fits-all.
For some patients—particularly those with very small, low-risk disease—active surveillance with endocrine therapy may be a reasonable option, especially as additional trial data continue to emerge.
Key Takeaways: LORETTA Trial: What Patients Should Know
- The study tested tamoxifen alone, without surgery, in carefully selected low-risk DCIS
- The trial did not meet a conservative, prespecified statistical threshold—but outcomes were still favorable for many participants
- Fewer than 10% developed invasive cancer at 5 years, and overall survival was excellent
- Imaging features, especially tumor size, were more predictive of risk than pathology alone
- The results support continued research into active surveillance for select DCIS patients
- LORETTA adds momentum toward more individualized, less aggressive care where appropriate
Looking Ahead
LORETTA is part of a broader shift in DCIS research—away from assuming that all DCIS requires the same treatment, and toward understanding who truly benefits from intervention and who may not.
Even when a trial does not meet its primary endpoint, it can still meaningfully advance patient care by sharpening risk assessment and expanding informed choice.
At DCIS Understood, we see LORETTA as another step toward a future where patients are offered options, not defaults, and where treatment intensity better matches actual risk.
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