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CHICAGO — Low-dose tamoxifen reduces the long-term risk for breast cancer in women treated for ductal carcinoma in situ (DCIS), but the benefits differ according to menopausal status.

In a pooled analysis of three studies, researchers found that postmenopausal women who took low-dose tamoxifen following DCIS saw a 10-year absolute risk reduction of 12.5% — driven by a substantial decrease in ipsilateral breast cancers.

In contrast, there was no clear protection against ipsilateral tumors among premenopausal women. There was, however, a 55% relative risk reduction in contralateral cancers, according to findings presented at the American Society of Clinical Oncology (ASCO) 2026.

“With a marked decrease in ipsilateral events, we recommend baby TAM for DCIS and residual disease control among postmenopausal women,” said lead investigator Andrea DeCensi, MD, PhD, medical oncologist at the Champalimaud Clinical Centre in Lisbon, Portugal.

For premenopausal women, he said, the strategy cannot be recommended for residual disease control, but the reduction in contralateral cancers suggests that low-dose tamoxifen still has benefits.

A trial to investigate that finding is warranted, DeCensi said.

The study, which was simultaneously published in the Journal of Clinical Oncology, confirms that baby TAM is a good alternative to full-dose 20 mg tamoxifen.

While the standard dose cuts the risk for invasive breast cancer after DCIS, concerns about side effects — including hot flashes, night sweats, and increased risks for venous thromboembolism and endometrial cancer — have greatly limited its use.

The results also provide a new layer by showing that the effects of low-dose tamoxifen clearly differ based on women’s menopausal status.

Kathy Miller, MD, breast cancer medical oncologist at Indiana University in Indianapolis, said the study is a win for baby TAM.

“It has significant benefit, especially for postmenopausal women, with substantially less toxicity,” she told Medscape Medical News.

And while ipsilateral cancers weren’t reduced among premenopausal women, low-dose tamoxifen can still be an option, according to Miller, who is also a Medscape Medical News contributor.

“If a premenopausal woman won’t accept full-dose therapy or struggles with toxicity, I would offer baby TAM as an alternative to nothing,” she said.

For the new analysis, DeCensi’s team pooled the results of two randomized trials — Trial 007 and Tam-01— and a single-center observational study that involved a total of 1545 women. The trials randomly assigned participants to 5 mg of tamoxifen once daily or a placebo group; in the observational study, women either received 10 mg of tamoxifen every other day or no endocrine therapy. Treatment lasted for 2-5 years.

All three studies were conducted in Italy, and most DCIS cases were detected clinically, not on routine screening mammograms. Most women in the analysis had DCIS, but 12% had atypical ductal hyperplasia or lobular carcinoma in situ. Nearly all (93%) underwent breast-conserving surgery, while over 40% had radiotherapy.

At a median follow-up of 9 years, ipsilateral breast cancers were more than halved among postmenopausal women on baby TAM — occurring in 22 of 335 women (6.6%) vs 63 of 401 (15.7%) in the control groups.

Among premenopausal women, contralateral tumors occurred in 21 of 448 (4.7%) on baby TAM compared with 35 of 335 control individuals (10.4%). Treatment made no significant difference in the risk for contralateral cancers among postmenopausal women: They occurred in 16 women on baby TAM (4.8%) and 22 in the control groups (5.5%).

The magnitude of the overall benefit with baby TAM was comparable to that reported in randomized trials of standard-dose tamoxifen, the researchers noted. There was no signal of increased risks for endometrial cancer or venous thrombosis.

The findings, Miller said, “should make prevention an acceptable option to many more women.”

DeCensi pointed to potential reasons for the findings on menopausal status. After menopause, low levels of circulating estrogen may make residual disease more sensitive to the effects of baby TAM’s partial estrogen receptor blockade, reducing the risk for ipsilateral cancer.

For premenopausal women, that partial blockade is likely insufficient to control residual disease — but it may be enough to interfere with new tumor formation in the contralateral breast. That benefit might be masked in older women, however, because their risk for contralateral disease after DCIS is relatively low.

The work was funded by the Italian Ministry of Health and others. DeCensi and Miller reported having no disclosures.

M. Alexander Otto is a physician assistant and award-winning journalist. He is also an MIT science journalism fellow. Email: aotto@medscape.net