Real-World Analysis May Clarify Role of Adjuvant Endocrine Therapy in Premenopausal HER2+ Breast Cancer

The reduced likelihood of receiving adjuvant endocrine therapy and ovarian suppression in addition to tamoxifen in premenopausal patients with hormone receptor (HR)–positive, HER2-positive breast cancer may indicate an unclear role for these treatments in this population, according to Jasmine Sukumar, MD. Through additional investigation of clinical pathologic factors and biomarkers, thereby improving clinical judgement, a consensus on the role of endocrine therapy in the HER2-positive subgroup could be reached.

Previous clinical trials evaluating the efficacy of ovarian suppression or hormonal therapy with either tamoxifen or exemestane vs tamoxifen alone in premenopausal women do not often include HER2-positive patients. Updated combined analysis of 2 significant trials in this space, the phase 3 SOFT (NCT00066703) and TEXT (NCT00066690) studies, showed that after 13 years of median follow-up, adjuvant exemestane plus ovarian suppression produced sustained reduction in the risk of recurrence vs tamoxifen plus ovarian suppression in patients with HR-positive early breast cancer. This benefit was most consistent in HER2-negative patients and in those with high-risk features.¹

Although the SOFT and TEXT trials did include a subset of HER2-positive patients, they commenced enrollment prior to adjuvant trastuzumab plus chemotherapy becoming the new standard of care in HER2-positive breast cancer and did not report on real-world treatment patterns.

Findings from a retrospective analysis of premenopausal women under 50 years were presented at the 2022 San Antonio Breast Cancer Symposium (SABCS). Results showed that 83% of patients had stage I/II breast cancer and 78% had node-positive disease (n = 818). Despite these patients displaying high-risk clinicopathologic features, 87% were treated with tamoxifen alone and 0.4%, 5.3%, and 6.9% were treated with ovarian suppression alone, tamoxifen plus ovarian suppression, and an aromatase inhibitor plus ovarian suppression, respectively.²

“This [research] highlights the wide variability in clinical use of ovarian suppression, and that more data is needed to guide endocrine therapy [approaches],” said Sukumar, who is an assistant professor in the Department of Breast Medical Oncology, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center in Houston.

In an interview with OncLive^®, Sukumar explains the purpose of analyzing endocrine therapy use in HR-positive/HER2-positive patients, key data presented from the retrospective analysis at SABCS, and the need for improved understanding of clinical indications for endocrine therapy in this breast cancer subtype.

OncLive: What was the impetus for researching real-world treatment patterns in this specific patient population?

Sukumar: HR-positive, HER2-positive breast cancer represents 10% of [patients with] breast cancer.In HER2-positive disease, the current standard of care is anti-HER2 therapy in combination with chemotherapy, but the optimal adjuvant endocrine therapy is unknown and the role of ovarian suppression is unclear. Most studies, including the phase 3 SOFT and TEXT studies, included HER2-positive patients, but these were underrepresented. Our goal was to further understand the real-world treatment patterns of ovarian suppression and endocrine therapy in this breast cancer subtype.

What key results from this study were shared at SABCS?

In this study, we performed a multi-institutional, retrospective analysis of premenopausal women with HR-positive, HER2-positive breast cancer. Data on ovarian suppression and other endocrine therapy use [was extrapolated from] the ASCO CancerLinQ^® discovery database. This study included 937 patients [under] 50, who received [prior] chemotherapy, anti-HER2 therapy, and endocrine therapy.

We found that the use of ovarian function suppression was uncommon in these patients. Only [12.6%] of patients received ovarian function suppression, and 87% received tamoxifen as an endocrine therapy of choice. This was surprising, because the use of ovarian suppression was uncommon in this breast cancer subtype in the real-world setting. There were no clinicopathologic features that predicted the use of ovarian suppression apart from age. Nodal status and [tumor] stage did not predict ovarian suppression use, which was [also] surprising.

What does this research indicate about the future of adjuvant endocrine therapy and ovarian suppression in this population?

To our knowledge, this is the first real-world study evaluating endocrine therapy [in this population]. The use of ovarian function suppression was uncommon in this population, and most providers were using tamoxifen as the endocrine therapy of choice.

[These findings] indicate that we need more data on the optimal adjuvant endocrine therapy and utility of ovarian suppression in these patients. This will [better] inform a personalized approach to therapy in these patients.

References

1. Regan MM, Walley BA, Fleming GF, et al. Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): update of the combined TEXT and SOFT trials. Cancer Res. 2022;82(suppl 4; abstr GS2-05). doi:10.1158/1538-7445.SABCS21-GS2-05
2. Sukumar JS, Sardesai S, Ni A, et al. Real-world treatment patterns of adjuvant endocrine therapy and ovarian suppression in premenopausal HR+/HER2+ breast cancer. Presented at 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX. Abstract P1-02-03.