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BERLIN — New data from the SOFT and TEXT trials showed that women with premenopausal invasive lobular carcinoma, than those with invasive ductal carcinoma, experience a greater magnitude of benefit when treated with the aromatase inhibitor exemestane plus ovarian suppression vs tamoxifen plus ovarian suppression and tamoxifen alone.

Overall, patients who received exemestane plus ovarian suppression had significantly longer disease-free survival than those who received the other two options, and the benefits of exemestane plus ovarian suppression were greater for those with invasive lobular carcinoma.

However, it's important to interpret these findings within the context of what we've learned from the overall SOFT/TEXT population of premenopausal women with hormone-sensitive early breast cancer, said Otto Metzger, MD, of the Dana-Farber Cancer Institute, Boston.

Bottomline: On average, exemestane plus ovarian suppression is better than tamoxifen plus ovarian suppression, which is better than tamoxifen alone, he said. But the "absolute treatment benefits are directly correlated to individual patient risks."

Metzger, who presented the data at the European Society for Medical Oncology (ESMO) Breast Cancer 2024 annual congress, reminded attendees that "as with many clinical questions, level I evidence from a phase 3 study will not be available, and therefore, clinical judgment remains critical in the selection of adjuvant therapy."

The new analysis looked at 3715 estrogen receptor–positive, human epidermal growth factor receptor 2–negative tumors from the SOFT and TEXT trials, 3370 of which were classified as invasive ductal carcinoma and 345 as invasive lobular carcinoma.

The results were adjusted for age, tumor size, nodal status, and Ki67 status. Luminal-A–like tumors were defined as Ki67 < 14%, and luminal-B–like tumors as Ki67 ≥ 14%. The primary study endpoint was disease-free survival.

Exemestane plus ovarian suppression showed a larger disease-free survival benefit over tamoxifen in women with invasive lobular carcinoma than in those with invasive ductal carcinoma (hazard ratio [HR], 0.32 vs HR, 0.71) at a median follow-up of 12 years.

The disease-free survival benefit persisted for those who received tamoxifen plus ovarian suppression vs tamoxifen alone but were not as strong (invasive lobular carcinoma: HR, 0.66; invasive ductal carcinoma: HR, 0.81).

In combined results from SOFT and TEXT, at a follow-up of 13 years, exemestane plus ovarian suppression showed a consistent benefit in patients with invasive lobular carcinoma (HR, 0.60) and invasive ductal carcinoma (HR, 0.70) compared with tamoxifen plus ovarian suppression, Metzger reported.

In subgroup analyses, the more pronounced treatment effects of exemestane plus ovarian suppression for invasive lobular carcinoma vs invasive ductal carcinoma appeared to be limited to luminal-A–like tumors, although this finding should be interpreted cautiously given the small numbers in this subgroup, he cautioned.

Discussant for the study Janice Tsang, MBBS, with The University of Hong Kong, Hong Kong, China, congratulated the authors for their work, which addresses the "unmet need for treatment improvement" in premenopausal women with invasive lobular carcinoma — the second most common histologic form of breast cancer, representing 5%-15% of all invasive breast cancers.

Tsang said the enhanced efficacy seen in the analysis provides "new hope" for this subgroup.

The remaining question, for premenopausal women with invasive ductal carcinoma, is whether they can just receive tamoxifen "to de-escalate the treatment and spare selected patients from side effects of ovarian suppression and aromatase inhibitor therapy," she said.

The studies were supported in part by Pfizer, Ipsen, TerSera, and AstraZeneca. Metzger had no relevant conflicts of interest. Tsang is on the speakers' bureau for AstraZeneca, Amgen, Daiichi Sankyo, Eisai, Gilead, Lilly, Lucence, Novartis, Pfizer, and Veracyte and serves as a medical advisor and consultant to De Novo and a grant panel reviewer for Pfizer.